TR201511406A2

TR201511406A2 - Oral formulations

Info

Publication number: TR201511406A2
Application number: TR2015/11406A
Authority: TR
Inventors: Erten Başaran Fatma
Original assignee: Fatma Erten Basaran
Priority date: 2015-09-14
Filing date: 2015-09-14
Publication date: 2017-03-21

Abstract

The present invention is related to the pharmaceutical composition/s which consist/s of a suitable active ingredient with analgesic and antipyretic property and/or pharmaceutically acceptable derivatives thereof in the prophylactic and/or symptomatic and/or therapeutic treatment of pain (mild, moderate, severe), arthralgia, fever, headache, migraine, dysmenorrhea, dental pain, tapping pain, throat pain, musculoskeletal-induced pain, menstrual pain, osteoarthritis, neuralgia, influenza, fever, symptomatic relief in fever and fever associated cold, the treatment of many bacterial and viral infections such as bronchitis, pharyngitis, tracheal bronchitis, sinusitis, pneumonia, otitis media, cervical adenitis, inflammation of tonsillis (tonsillitis), postimmunization (post-vaccination) reactions.

Description

TARIFNAME ORAL FORMÜLASYONLAR BULUSUN ILGILI OLDUGU ALAN Mevcut bulus; agri (hafif, orta, siddetli), artralji, ates, bas agrisi, migren, dismenore, dis agrisi, dis çekme agrisi, bogaz agrisi, kas-iskelet kaynakli agri, menstrual agrilar, osteoartrit, nevralji, influenza, ates ve atesle birlikte görülen soguk alginliginda semptomatik rahatlama, bronsit, faranjit, trakeal bronsit, sinüzit, pnömani, orta kulak iltihabi, servikal adenit gibi birçok bakteriyel ve virütik enfeksiyonlarin tedavisinde, tonsilit (bademcik iltihabi), postimmünizasyon (asilanma sonrasi) reaksiyonlarinin profilaktik ve/veya semptomatik ve/veya terapötik tedavisinde kullanilmak üzere anal jezik ve antipiretik özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farrnasötik bilesim/ler ile ilgilidir. DESCRIPTION ORAL FORMULATIONS FIELD OF THE INVENTION The present invention; pain (mild, moderate, severe), arthralgia, fever, headache, migraine, dysmenorrhea, dental pain, tooth extraction pain, sore throat, musculoskeletal pain, menstrual pain, in osteoarthritis, neuralgia, influenza, fever and cold associated with fever symptomatic relief, bronchitis, pharyngitis, tracheal bronchitis, sinusitis, pneumonia, middle ear In the treatment of many bacterial and viral infections such as inflammation, cervical adenitis, tonsillitis (tonsillitis), postimmunization (post vaccination) reactions analgesic for use in the prophylactic and/or symptomatic and/or therapeutic treatment and the appropriate active substance with antipyretic properties and/or pharmaceutically acceptable relates to pharmaceutical composition(s) containing derivatives thereof.

Mevcut bulus; analjezik ve antipiretik özellikteki etken maddenin Parasetamol, N-(4- hidroksifenil)asetamid (Formül I) ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesim/ler ile ilgilidir. The present invention; Paracetamol, N-(4- hydroxyphenyl)acetamide (Formula I) and/or pharmaceutically acceptable derivatives relates to the pharmaceutical composition(s) for which it is used.

Formül 1: Ayrica bulus, Parasetamol ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oral uygulama için uygun olan formülasyonlarini ve profilaktik ve/veya semptomatik ve/veya terapötik kullanimlarini kapsamaktadir. ÖNCEKI TEKNIK (TEKNIGIN BILINEN DURUMU) Asetaminofen ya da yaygin olarak bilinen adiyla parasetamol, paraaminofenol türevi analjezik ve antipiretik bir ilaçtir. Parasetamol agizdan alindiginda gastrointestinal sistemde hizla emilir. Parasetamol bütün dokulara hizla dagilir. Gastrointestinal sistemde yan etkisinin hemen hemen olmamasi, güvenilirligi ve de gebelerde kullanilabilmesi parasetamolun her zaman ön planda kalmasini ve klasik bir analjezik olmasini saglar.Formula 1: In addition, the invention relates to the use of Paracetamol and/or its pharmaceutically acceptable derivatives. formulations of the pharmaceutical compositions for which it is used, suitable for oral administration, and includes prophylactic and/or symptomatic and/or therapeutic uses. PRIOR ART (KNOWN STATE OF THE ART) Acetaminophen or commonly known as paracetamol, paraaminophenol derivative It is an analgesic and antipyretic drug. When paracetamol is taken orally, gastrointestinal is rapidly absorbed in the system. Paracetamol is rapidly distributed to all tissues. In the gastrointestinal tract almost no side effects, safety and can be used in pregnant women It ensures that paracetamol is always at the forefront and is a classic analgesic.

Parasetamol (Asetaminofen) dünyada en çok kullanilan analjeziklerden biridir. 1000mg kadar tedavi dozunda hem akut hem kronik durumlarda hafif agridan orta agriya kadar çogu agrida reçete edilen bir analjeziktir [Nikles CJ, Yellaiid M, Del Mar C, Wilkinson D, The role of paracetainol in chronic pain: aii evidence-based approach.Ani .I Ther 2005;12(l):80-9l. , Sachs CJ. Oral dozlarda hem opioidlerden hemde NSAII”den daha düsük yan etkiye (nefrotoksite, hepatotoksite, vs) sahiptir. Çogunlukla oral ya da rektal yolla kullanilmasina ragmen son zamanlarda Avrupa ülkelerinde intravenöz yolla kullanim sikligi giderek artmaktadir of paracetamol, NSAIDS or their combination in postoperative pain management: a qualitative review. Br J Çocuk polikliniklerine basvuru nedenleri içinde en sik karsilasilan sorunlardan biri atestir. Çocuklarda her zaman olmasa bile tedavinin yönetimi esnasinda atesin düsürülmesi bazen öncelikli hedefler arasinda yer alabilir. Çocuklarda bu amaçla tüm dünyada siklooksijenaz inhibitörleri kullanilmaktadir. Salisilik asit ve nonsteroid antiintlamatuar (NSAI) ilaçlar hem santral hem periferal olarak prostaglandin (PG) sentezini inhibe ederken, parasetamol esas olarak merkezi etkilidir. Parasetamolün ates düsürücü etkisi beyinde prostoglandin sentezinin inhibisyonu ile gerçeklesir. Paracetamol (Acetaminophen) is one of the most widely used analgesics in the world. 1000mg Mild pain to moderate pain in both acute and chronic conditions at a therapeutic dose of up to is an analgesic most prescribed for pain [Nikles CJ, Yellaiid M, Del Mar C, Wilkinson D, The role of paracetainol in chronic pain: aii evidence-based approach.Ani .I Ther 2005;12(l):80-9l. , Sachs CJ. Oral lower side effects (nephrotoxicity, nephrotoxicity) than both opioids and NSAIDs at doses hepatotoxicity, etc.). Although it is mostly used orally or rectally, the last In recent times, the frequency of intravenous use is increasing in European countries. of paracetamol, NSAIDS or their combination in postoperative pain management: a qualitative review. Br J Fever is one of the most common causes of admission to pediatric outpatient clinics. Fever reduction is sometimes, but not always, in children during the management of therapy. may be among the priority targets. For this purpose in children, cyclooxygenase is used all over the world. inhibitors are used. Salicylic acid and nonsteroidal anti-inflammatory (NSAI) drugs Paracetamol inhibits prostaglandin (PG) synthesis both centrally and peripherally. mainly centrally effective. The antipyretic effect of paracetamol is prostaglandin in the brain. occurs by inhibition of its synthesis.

US 6,939,550 nolu patent dökümanina göre; antihistaminik surup fonnülasyonlari tek bir doz ile birden fazla tedavi sonucu elde etmek için siklikla diger ilaçlari da içerir.According to the patent document US 6,939,550; antihistamine syrup formulations It often includes other drugs to achieve multiple treatment results with one dose.

Antihistamin ile birlikte bulunan tipik ilaçlar sunlardir: örnegin psödoefedrin ya da fenilpropanolamin (rinit ve üst solunum yolu enfeksiyonlari gibi rahatsizliklarin eslik ettigi üst solunum yolu tikanikligini hafifletmek için) ve analjezikler Örnegin aspirin, asetaminofen, ibuprofen, naproksen ya da ketoprofen (asetaminofen Örnegi disinda, inflamasyonu azaltmak ve agriyi dindirmek için). Typical drugs associated with an antihistamine are, for example, pseudoephedrine or phenylpropanolamine (accompanied by diseases such as rhinitis and upper respiratory tract infections) to relieve upper airway obstruction) and analgesics such as aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen (with the exception of the acetaminophen Example, to reduce inflammation and relieve pain).

EP 2012765 nolu patent dokümaninda soguk alginligi, grip, alerji, sinüzit ve rinit gibi solunum yolu hastaliklarinin tedavisinde kullanilan sivi bilesimlerden bahsedilmektedir. In the patent document numbered EP 2012765, such as cold, flu, allergy, sinusitis and rhinitis Liquid compositions used in the treatment of respiratory tract diseases are mentioned.

Bu sivi bilesimler belirli pH degerine sahip olup, fenilefrin ve asetaminofen içermektedir. These liquid compositions have a certain pH value and contain phenylephrine and acetaminophen.

US 8568775 nolu patent dökümaninda parasetamol içeren tablet forrnülasyonundan bahsedilniektedir.From the tablet formulation containing paracetamol in the patent document US 8568775 is mentioned.

BULUSUN AÇIKLAMASI Mevcut bulus; agri (hafif, orta, siddetli), artralji, ates, bas agrisi, migren, dismenore, dis agrisi, dis çekme agrisi, bogaz agrisi, kas-iskelet kaynakli agri, menstrual agrilar, osteoartrit, nevralji, iniluenza, ates ve atesle birlikte görülen soguk alginliginda semptomatik rahatlama, bronsit, faranjit, trakeal bronsit, sinüzit, pnömani, orta kulak iltihabi, servikal adenit gibi birçok bakteriyel ve virütik enfeksiyonlarin tedavisinde, tonsilit (bademcik iltihabi), postimmünizasyon (asilanma sonrasi) reaksiyonlarinin profilaktik ve/veya semptomatik ve/veya terapötik tedavisinde kullanilmak üzere analjezik ve antipiretik özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesim/ler ile ilgilidir. DESCRIPTION OF THE INVENTION The present invention; pain (mild, moderate, severe), arthralgia, fever, headache, migraine, dysmenorrhea, dental pain, tooth extraction pain, sore throat, musculoskeletal pain, menstrual pain, in osteoarthritis, neuralgia, influenza, fever and cold associated with fever symptomatic relief, bronchitis, pharyngitis, tracheal bronchitis, sinusitis, pneumonia, middle ear In the treatment of many bacterial and viral infections such as inflammation, cervical adenitis, tonsillitis (tonsillitis), postimmunization (post vaccination) reactions analgesic for use in the prophylactic and/or symptomatic and/or therapeutic treatment and the appropriate active substance with antipyretic properties and/or pharmaceutically acceptable relates to pharmaceutical composition(s) containing derivatives thereof.

Mevcut bulusun bir diger yönü; oral kullanilmak üzere bir analjezik ve antipiretik özellikteki etken madde ve/veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir uygun yardimci maddeleri içeren farmasötik bilesim/ lerin hazirlanmasiyla ile ilgilidir. Another aspect of the present invention is; an analgesic and antipyretic for oral use active ingredient and/or pharmaceutically acceptable derivatives, and pharmaceutical containing suitable pharmaceutically acceptable excipients relates to the preparation of the composition/s.

Bulusta, analjezik ve/veya antipiretik özellik gösteren etken madde/ler asetilsalisilik asit, aloksiprin, kolin salisilat, sodyum salisilat, salisil salsalat, etenzamid, morfolin salisilat, dipirosetil, benorilat, diflunisal, potasyum salisilat, guasetisal, karbasalat kalsiyum, imidazol salisilat, fenazon, metamizol, aminofenazon, propifenazon, nifenazon, parasetamol, fenasetin, busetin, propasetamol, rimazolyum, glafenin, floktafeniii, viminol, nefopam, flupirtin, zikonotid, metoksifluran, nabiksimols, morfin, opium, hidromorfon, nikomorfin, oksikodon, dihidrokodein, diamorfin, papaveretum, ketobemidon, petidin, fentanil, dekstromoramid, piritramid, dekstropropoksifen, bezitramid, pentazosin, fenazosin, buprenorfin, butorfanol, nalbufin, tilidin, tramadol, dezosin, meptazinol, tapentadol, dihidroergotamin, ergotamin, metisergid, lisurid, flumedrokson, sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, frovatriptaii, pizotifen, klonidin, iprazokrom, dimetotiazin, oksetoron, zukapsaisin ve/veya farmasötik olarak kabul edilebilir türevleri arasindan tercihen Parasetamol olarak seçilir. In the invention, the active ingredient/s acetylsalicylic acid, which has analgesic and/or antipyretic properties, aloxiprine, choline salicylate, sodium salicylate, salicyl salsalate, ethenzamide, morpholine salicylate, dipyrocetyl, benorilate, diflunisal, potassium salicylate, guacetisal, carbasalate calcium, imidazole salicylate, phenazone, metamizole, aminophenazone, propifenazone, niphenazone, paracetamol, phenacetin, busetin, propacetamol, rimazolium, glafenin, floctafeniii, viminol, nefopam, flupirtine, ziconotide, methoxyflurane, nabiximols, morphine, opium, hydromorphone, nicomorphine, oxycodone, dihydrocodeine, diamorphine, papaveretum, ketobemidone, pethidine, fentanyl, dextromoramide, pyriteramide, dextropropoxyphene, bezitramide, pentazocine, phenazosin, buprenorphine, butorphanol, nalbuphine, tilidine, tramadol, dezosine, meptazinol, tapentadol, dihydroergotamine, ergotamine, methysergid, lisuride, flumedroxone, sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan, frovatriptaii, pizotifen, as clonidine, iprazochrome, dimethothiazine, oxetorone, zucapsaicin and/or pharmaceutical it is preferably selected as Paracetamol among its acceptable derivatives.

Bulusta “farmasötik olarak kabul edilebilir türevleri” terimi ile farmasötik olarak kabul edilebilir uygun tuzlar, esterler, solvatlar, hidratlar, kompleksler, polimorflar, enantiyomerler, önilaçlar, asit adisyon tuzlari, analoglar, izomerler, rasematlar, amidler, enantiyomer tuzlari, bazik tuzlar, konjugeler, tautomerler, anhidratlar, anhidritler, bazlar, asitler, eterler, kristal ve amorf formlar veya serbest formlarindan bir veya daha fazlasi ifade edilmektedir. In the invention, the term "pharmaceutically acceptable derivatives" is defined as pharmaceutically acceptable. Suitable salts, esters, solvates, hydrates, complexes, polymorphs, enantiomers, prodrugs, acid addition salts, analogs, isomers, racemates, amides, enantiomer salts, basic salts, conjugates, tautomers, anhydrates, anhydrides, bases, one or more of acids, ethers, crystalline and amorphous forms or free forms is expressed.

Oral uygulama için hazirlanan fannasötik bilesim kati ya da sivi dozaj fonnlarinda olabilir.The pharmaceutical composition for oral administration may be in solid or liquid dosage forms.

Bu dozaj formlari; tablet (çignenebilir, agizda çözünen, dagilabilen, suda dagilabilen, film kapli, çift katli, çok katli, enterik kapli, mini, kontrollü salimli, sürekli salimli, hemen salimli, uzatilmis saliirili, geciktirilmis salimli, degistirilmis saliinli, modifiye salimli), kapsül (sert, yumusak, enterik kapli, film kapli, kontrollü salimli, sürekli salimli, hemen salimli, uzatilmis salimli, geciktirilmis salimli, degistirilmis salimli, modifiye salimli), toz, granül, kaplet, disk, agizda çözünen film, yigin toz (çok dozlu), pellet, sase, suda dagilabilen toz, suda dagilabilen granül, efervesan tablet, efervesan granül, efervesan toz formu, jelül, pilül, surup, solüsyon, süspansiyon, eliksir, damla, posyon, emülsiyon veya sprey gibi bir dozaj sekli halinde formüle edilebilir. These dosage forms are; tablet (chewable, mouth-soluble, dispersible, water-dispersible, film coated, bilayer, multilayer, enteric coated, mini, controlled release, sustained release, immediate release, extended release, delayed release, modified saline, modified release), capsule (hard, soft, enteric-coated, film-coated, controlled-release, sustained-release, immediate release, extended release, delayed release, modified release, modified release), powder, granule, caplet, disc, oral film, bulk powder (multidose), pellet, sachet, aqueous dispersible powder, water dispersible granule, effervescent tablet, effervescent granule, effervescent powder form, gel, pill, syrup, solution, suspension, elixir, drop, position, emulsion or may be formulated in a dosage form such as a spray.

Dogrudan dogruya ilaç olarak veya tabletlerin hazirlanmasinda ön basamak olarak kullanilan birbirine kenetlenmis asimetrik agregatlara granüle denir. Granüle çekirdegi az veya çok poröz, kürevi ve silindir seklinde olabilir. Birden fazla küçük çekirdekten olusur.Directly as a medicine or as a preliminary step in the preparation of tablets Interlocking asymmetric aggregates used are called granules. Less granulated kernel or very porous, spherical and cylindrical. It consists of multiple small nuclei.

Toz maddelerle çesitli sekil ve görünüste hazirlanan farkli parça büyüklügünde agregatlardir. It is prepared with powder materials in various shapes and apparently in different piece sizes. are aggregates.

Tablet hazirlanmasinda toz veya granüle kullanmanin bazi üstünlük ve sakincalari su sekildedir: o Toz karisimi serbest akabilen bir sekle sokmak, - Farkli toz maddelerden olusan karisima ortak ve tek bir dansite kazandirmak, o Ayrismayan homojen bir karisim olusturmak, - Etkin maddenin ve basim kütlesinin basilabilme özelligini gelistirmek, o Etkin madde salim hizini kontrol edebilmek, o Homoj en dagilim ve birim doz dogrulugunu temin etmek, o Tozlanmanin ve kontaminasyon riskinin önlenmesi ve tozlanma ile doz kaybinin önüne geçmek. Some advantages and disadvantages of using powder or granules in tablet preparation are water. is as follows: o Putting the powder mixture in a free flowing form, - Gaining a common and single density to the mixture consisting of different powder substances, o Forming a homogeneous mixture that does not separate, - To improve the printing ability of the active substance and the printing mass, o To be able to control the active substance release rate, o To ensure homogeneous distribution and unit dose accuracy, o Prevention of dusting and contamination risk and loss of dose by dusting prevent.

Granüle hazirlanmasinda içerdikleri etkin maddenin niteliklerine göre; kuru granülasyon yöntemi ve yas granülasyon yönteminden faydalanilmaktadir.According to the properties of the active substance they contain in the preparation of granules; dry granulation method and wet granulation method are used.

Dozaj formlarinin hazirlanmasinda birçok teknikten yararlanilmaktadir. Bunlardan biri de granülasyon yöntemidir. Granülasyon; ince toz partiküllerin büyümesi seklinde tanimlanmaktadir, Farmasötik amaçli granülasyon; tabletleme için bir ön hazirlik asamasidir, ayni zamanda, sert j elatin kapsüle doldurma veya granülün bir final ürün olarak bir pakete yerlestirilerek kullanimi amaciyla da uygulanmaktadir. Many techniques are used in the preparation of dosage forms. one of them granulation method. Granulation; as the growth of fine dust particles granulation for pharmaceutical purposes; a preparation for tableting This is the stage of filling hard gelatin capsules or granules as a final product. It is also applied for the purpose of being placed in a package.

Granülasyonun amaci, karisima istirak eden toz maddenin partiküllerinin birim ilacinin % miktarlarina esdeger olacak agirlikta bir ünite olusturmaktir. Farmasötik toz karisimlarin (etken madde veya yardimci maddeler) ayrismalarini engelleyerek bir ünite içerisinde homojen bir sekilde kalmalarini saglamak gerekmektedir bu da granülasyon ile mümkündür. The purpose of the granulation is to give the unit drug % of the particles of the powder substance participating in the mixture. is to create a unit of weight that will be equivalent to the quantities. Pharmaceutical powder mixes (active substance or auxiliary substances) in a unit by preventing their separation. It is necessary to ensure that they remain in a homogeneous form, this is achieved by granulation. possible.

Granülasyonda seçilecek yöntemler 3 ana kategoride siniflandirilabilir: yas granülasyon, kuru granülasyon ve diger granülasyon yöntemleri. The methods to be chosen in granulation can be classified in 3 main categories: wet granulation, dry granulation and other granulation methods.

Yas Granülasyon: Yas granülasyon yönteminde, yüksek hizli akiskan yatak granülasyon, püskürterek kurutma ve ekstrüsyon pelletleme yöntemleri kullanilmaktadir. Yas granülasyonda, etken madde ve baglayici madde (solüsyon) belirli sürede karistirilir, yas olarak elenir ve akiskan yatakli kurutucuda kurutulur. Kurutulan bu karisim diger dolgu maddeleri ile birlikte belirli bir homojenlige gelinceye kadar karistirilir. Karisimin son 3-5 dakikasinda kaydirici eklenir. Elde edilen final karisimdan örnekler alinir ve laboratuvara gönderilir. Laboratuvar sonucuna göre tablet basimina yada istenilen farmasötik form için asamalara geçilebilir.Age Granulation: In the wet granulation method, high speed fluidized bed granulation, spray drying and extrusion pelletizing methods are used. Mourning In granulation, the active ingredient and the binder (solution) are mixed for a certain period of time. sieved and dried in a fluidized bed dryer. This dried mixture is the other filling. It is mixed with the ingredients until it reaches a certain homogeneity. My wife's last 3-5 slider is added in minutes. Samples are taken from the final mixture obtained and sent to the laboratory. sent. According to the results of the laboratory, for tablet compression or for the desired pharmaceutical form. stages can be passed.

Yas granülasyon yöntemleri: 1. Yas granülasyori yöntemi (Klasik yöntem) 2. Akiskan yatak yöntemiyle granülasyon 3. Spray-Drying (püskürterek kurutma) yöntemi ile granülasyon 4. Mikrogranülasyon yöntemi . Ekstrüsyon-Spheronizasyon yöntemi 6. Yüksek hiza sahip karistiricilarla granüle hazirlama yöntemi Yas granülasyon islemi su sirayi izlemektedir: - Etken maddenin (gerekli görülür ise) ögütülmesi, - Toz maddelerle karistirilmasi, - Baglayici ilavesiyle toz karisimin partiküllerinin kümelesmesinin saglanmasi, (Bu isleme granülasyon denir.) - Kümelesmis partiküllerin yas olarak elenmesi, - Elenmis toz karisiminin kurutulmasi kurutma islemde yaygin alarak akiskan yatakli kurutucular kullanilmasi, - Kurutma isleminden sonra kuru ögütme yapilmasi, - Çift konik ya da V tipi karistiricilarda homojenize edilmesi - Olusan bu karisima kaydirici ilave edilerek 5 dakika daha karistirilmasi, (Bu karisima final ürün denir.) - Tablet basimina yada istenilen farmasötik form için asamalara geçilmesidir. Age granulation methods: 1. Age granulation method (Classical method) 2. Granulation by fluidized bed method 3. Granulation by Spray-Drying method 4. Microgranulation method . Extrusion-Spheronization method 6. Method of preparing granules with high-level mixers The wet granulation process is as follows: - Grinding the active ingredient (if necessary), - Mixing with powder substances, - Ensuring the aggregation of the particles of the powder mixture with the addition of binder, The process is called granulation.) - Screening of agglomerated particles as wet, - Drying of the sifted powder mixture is common in the drying process using bed dryers, - Dry grinding after drying, - Homogenizing in double conical or V type mixers - Adding lubricant to this resulting mixture and mixing for another 5 minutes, (This the mixture is called the final product.) - It is the transition to tablet pressing or the stages for the desired pharmaceutical form.

Kuru Granülasyon: Kuru granülasyon yönteminde, ön kompresyon ve silindirler arasi sikistirma yöntemleri kullanilmaktadir. Kuru granülasyonda genellikle formüldeki kaydiricinin l/3”ü diger toz karisimlarina karistirilir. Bunun nedeni tozlarin silindirlere yapismasini engeller. Kaydiricinin geri kalani kuru granülasyondan sonra karisima eklenir ve 3-5 dakika karistirilir. Karisim sonrasinda olusan final karisimdan örnekler alinir ve çesitli testler için laboratuvara gönderilir. Laboratuvar sonucuna göre tablet basimina geçilebilir. Dry Granulation: In the dry granulation method, pre-compression and inter-roll compression methods are used. In dry granulation, it is usually 1/3 of the lubricant is mixed with other powder mixtures. This is because dust gets into the cylinders. prevents it from sticking. The remainder of the lubricant is added to the mix after dry granulation. and stirred for 3-5 minutes. Samples are taken from the final mixture formed after the mixture and It is sent to the laboratory for various tests. According to the laboratory results, tablet compression passable.

Suruplar, sakkaroz veya diger sekerlerin yüksek derisimdeki çözeltilerinin içindeki etkin madde ve yardimci maddelerin çesitli yöntemlerle çözünmesi ile olusmus sivi ilaç sekilleridir. Sadece % 64 oraninda sakkarozun suda çözünmesi ile hazirlanmis suruplara Basit Surup (Sirupus Simplex) denir. Suruplar, USP 245e göre % 85 a/h de seker içerirler.Syrups are active in high skin solutions of sucrose or other sugars. liquid medicine formed by the dissolution of substances and auxiliary substances by various methods are shapes. Syrups prepared by dissolving only 64% sucrose in water It is called Simple Surup (Sirupus Simplex). The syrups contain 85% w/v sugar according to USP 245.

Suruplara seker ve diger tatlandiricilarin yani sira kristallenmeyi engellemek, çözünürlügü ve tadi degistirmek için sorbitol veya gliserin ve koku vermek için aromatik maddeler ilave Suruplaiin hazirlama yöntemleri: 1. Sicakta veya sogukta basit çözündürme yoluyla hazirlananlar 2. Ekstre ve tentürlerle hazirlanan suruplar 3. Maserasyon ve di jestiyon yöntemi ile hazirlananlar 4. Meyva usareleri ile hazirlanan suruplar . Kimyasal yolla hazirlananlar 6. Perkolasyon yolu ile hazirlananlar 7. Tekrar çözündürme yöntemi ile hazirlananlar olarak siralanabilir. In addition to sugar and other sweeteners, it is added to syrups to prevent crystallization, increase solubility. and adding sorbitol or glycerin to alter the taste and aromatic substances to impart flavor Preparation methods of Suruplai: 1. Prepared by simple dissolution in hot or cold 2. Syrups prepared with extracts and tinctures 3. Prepared by maceration and digestion method 4. Syrups prepared with fruit juices . Chemically prepared 6. Those prepared by percolation 7. Resolution method can be listed as those prepared with.

Mevcut bulusta oral yolla uygulamaya yönelik farmasötik surup formülasyonu; farmasötik olarak kabul edilebilir uygun etken madde/ler yaninda en az bir antiinikrobiyal koruyucu, en az bir tatlandirici madde, en az bir sivag, en az bir tamponlayici ajan, en az bir pH ayarlayici ajan, en az bir boyar madde, en az bir aroma verici ajan ve çözücünün de dahil oldugu gruptan seç-ilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. The pharmaceutical syrup formulation for oral administration in the present invention; pharmaceutical at least one antimicrobial preservative in addition to the appropriate active ingredient/s, at least one sweetening agent, at least one liquid, at least one buffering agent, at least one pH setting agent, at least one dyestuff, at least one flavoring agent and solvent. Defines a compound that may contain one or more excipients selected from the group it is in.

Mevcut bulusta oral yolla uygulamaya yönelik farmasötik tablet formülasyonu; farmasötik olarak kabul edilebilir uygun etken madde/ler yaninda en az bir dagitici/baglayici madde, en az bir koruyucu madde, en az bir kaydirici madde ve en az bir granülasyon sivisinin da dahil oldugu gruptan seçilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. The pharmaceutical tablet formulation for oral administration in the present invention; pharmaceutical at least one dispersant/binding agent, as well as suitable active ingredient(s) that can be accepted as at least one preservative, at least one lubricant, and at least one granulation fluid. a composition that may contain one or more excipients selected from the group it belongs to defines.

Bulusta “antimikrobiyal koruyucu” terimi, kontaminasyonu önleyen ve ardindan mikrobiyolojik üremeyi engelleyen maddeler olarak ifade edilmektedir. Antimikrobiyal koruyucu madde olarak; metil parahidroksibenzoat, etil parahidroksibenzoat, propil parahidroksibenzoat, butil parahidroksibenzoat gibi parabenler, sodyum benzoat, potasyum sorbat, sodyum metil paraben, sodyum propil paraben, edetatin tuzlari (etilendiaminetetrasetik asit ya da disodyum edetat gibi EDTA°nin tuzlari), gliserin, benzalkonyum klorür veya bunlarin karisimlari kullanilabilir. Bulusta surup formülasyonunda antimikrobiyal koruyucu olarak tercihen sodyum metil paraben ve sodyum propil paraben antimikrobiyal koruyucu sinerjisti olarak tercihen potasyum sorbat kullanilmaktadir. Ayrica bulusta tablet formülasyonunda koruyucu madde olarak tercihen potasyum sorbat kullanilmaktadir. Bulusta surup formülasyonunda kullanilan antimikrobiyal koruyucu ve antimikrobiyal koruyucu sinerjisti madde miktari gr/ 150m1“de 0.001-10 gr araligindadir. Bulusta tablet formülasyonunda kullanilan koruyucu madde Bulusta “tatlandirici madde” terimi etken maddenin kötü tadini ortadan kaldirmak amaciyla kullanilan dogal ve yapay maddeler olarak ifade edilmektedir. Tatlandirici madde olarak; seker, gliserin, misir pekmezi, fruktoz, sukraloz, sukroz, potasyum asesülfam, sodyum sakkarin, sodyum sakkarin dihidrat, mannitol, aspartam, sodyum siklamat, sorbitol veya bunlarin karisimlari kullanilabilir. Bulusta tatlandirici madde olarak tercihen sukroz ve sodyum sakkarin dihidrat kullanilmaktadir. Bulusta kullanilan tatlandirici madde miktari gr/150m1“de 0.01-80 gr araligindadir. In the invention, the term "antimicrobial preservative" refers to those that prevent contamination and subsequently It is expressed as substances that inhibit microbiological growth. antimicrobial as a preservative; methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parabens such as parahydroxybenzoate, butyl parahydroxybenzoate, sodium benzoate, potassium sorbate, sodium methyl paraben, sodium propyl paraben, edetatin salts (salts of EDTA such as ethylenediaminetetracetic acid or disodium edetate), glycerin, benzalkonium chloride or mixtures thereof may be used. Surr at the find sodium methyl paraben and preferably sodium methyl paraben as antimicrobial preservative in its formulation. preferably potassium sorbate as sodium propyl paraben antimicrobial preservative synergist is used. It is also preferred as a preservative in tablet formulation in the invention. potassium sorbate is used. used in the formulation of syrup in the invention amount of antimicrobial preservative and antimicrobial preservative synergist substance in gr/ 150m1 It is in the range of 0.001-10 gr. Preservative used in tablet formulation of the invention In the invention, the term "flavoring agent" is used to remove the bad taste of the active ingredient. It is expressed as natural and artificial substances used for the purpose. sweetening agent aspect; sugar, glycerin, molasses, fructose, sucralose, sucrose, potassium acesulfame, sodium saccharin, sodium saccharine dihydrate, mannitol, aspartame, sodium cyclamate, sorbitol or mixtures of these can be used. Preferably sucrose as sweetening agent in the invention and sodium saccharin dihydrate are used. Sweetening agent used in the invention amount is between 0.01-80 gr per gr/150m1.

Bulusta sivag olarak; makrogol türevleri, vazelin, mumla modifiye vazelin, sivi vazelin, beyaz vazelin, lanolin veya lanolin türevleri, hint yagi, hindistan cevizi yagi, zeytinyagi, pamuk tohumu yagi gibi bitkisel yaglar, polietilen glikol, parafin, anhidröz, beyaz yumusak parafin, gliserol, propilen glikol veya bunlarin karisimlari kullanilabilir. Bulusta sivag olarak tercihen gliserol ve propilen glikol kullanilmaktadir. Bulusta kullanilan sivag miktari gr/lSOdee l-l40 gr araligindadir. As sivag in the invention; macrogol derivatives, petrolatum, wax modified vaseline, liquid petrolatum, white petrolatum, lanolin or lanolin derivatives, castor oil, coconut oil, olive oil, vegetable oils such as cottonseed oil, polyethylene glycol, paraffin, anhydrous, white soft paraffin, glycerol, propylene glycol or their mixtures can be used. in the find Glycerol and propylene glycol are preferably used as the substrate. Sivag used in the invention the amount is in the range of gr/lSOdee l-140 gr.

Bulusta tamponlayici ajan olarak; mono sodyum sitrat, sitrik asit, sitrik asit anhidrus, sodyum sitrat dihidrat, sodyum klorür, sitrik asit monohidrat, sodyum hidrojen karbonat (sodyum bikarbonat), sodyum karbonat, sodyum glisin karbonat, potasyum karbonat, potasyum bikarbonat veya bunlarin karisimlari kullanilabilir. Bulusta tamponlayici ajan olarak tercihen sitrik asit anhidrus ve sodyum sitrat dihidrat kullanilmaktadir. Bulusta kullanilan tamponlayici ajan miktari gr/ 150mlçde 0.001-10 gr araligindadir, Bulusta pH ayarlayici ajan olarak; hidroklorik asit, sodyum hidroksit, sodyum karbonat, sodyum bikarbonat, sodyum silikat, disodyuin ortofosfat, kalsiyum karbonat, magnezyum karbonat, magnezyum hidroksit, magnezyum alüminat, dietanol amin, sodyum aljinat, etilendiamin, meglümin, mono sodyum sitrat, sitrik asit, sitrik asit monohidrat, sodyum sitrat dihidrat veya bunlarin karisimlari kullanilabilir. Bulusta pH ayarlayici ajan olarak sitrik asit monohidrat kullanilmaktadir. As a buffering agent in the invention; mono sodium citrate, citric acid, citric acid anhydrous, sodium citrate dihydrate, sodium chloride, citric acid monohydrate, sodium hydrogen carbonate (sodium bicarbonate), sodium carbonate, sodium glycine carbonate, potassium carbonate, potassium bicarbonate or mixtures of these can be used. buffering agent in the invention preferably citric acid anhydrous and sodium citrate dihydrate are used. in the find The amount of buffering agent used is in the range of 0.001-10 g per gr/ 150 ml, As a pH adjusting agent in the invention; hydrochloric acid, sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol amine, sodium alginate, ethylenediamine, meglumine, mono sodium citrate, citric acid, citric acid monohydrate, sodium citrate dihydrate or mixtures thereof can be used. As a pH adjusting agent in the invention citric acid monohydrate is used.

Bulusta “boyar madde” terimi hos bir görünüs veren ve iki formülasyon arasinda optik olarak ayirt edilme saglayan maddeler olarak ifade edilmektedir. Boyar madde olarak, bunlarla sinirli kalmamakla birlikte, sari demir oksit, kirmizi demir oksit gibi demir oksit pigmentleri, ß-karoten, kirmizi pancar tozu, klorofil, tartrazin, sari portakal, kinolin sarisi, eritrosin, titanyum dioksit, karamel, kirmizi gida boyasi (food red & ponceu 4R) veya bunlarin karisimlari kullanilabilir. Bulusta boyar inadde olarak tercihen kirmizi gida boyasi (food red & ponceu 4R) kullanilmaktadir. Bulusta kullanilan boyar madde miktari gr/ 150ml“de 0.001-10 gr araligindadir. In the invention, the term "dyestuff" is a pleasant-looking and optically intermediate between the two formulations. are expressed as substances that provide discrimination. As a dyestuff, iron oxide such as, but not limited to, yellow iron oxide, red iron oxide pigments, ß-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide, caramel, food red color (food red & ponceu 4R) or mixtures of these can be used. In the invention, preferably red food dye as dyestuff. (food red & ponceu 4R) is used. The amount of dyestuff used in the invention gr/ It is in the range of 0.001-10 gr in 150ml.

Bulusta “aroma verici ajan” terimi, hasta tarafindan alimini kolaylastirmak amaciyla formülasyona ilave edilen maddeler olarak ifade edilinektedir. Aroma verici ajan olarak; hem suni hem dogal meyve esanslari (kiraz, üzüm, portakal, portakal(s1vi), çilek, visne vb.), nane kokusu (nane sekeri, mentol), kahve, kakao, tarçin, vanilya, suni vanilya, çikolata, suni çikolata, sakiz, pepperrnint veya bunlarin karisimlari kullanilabilir. Bulusta aroma verici ajan olarak tercihen visne esansi kullanilmaktadir. Bulusta kullanilan aroma verici ajan miktari gr/150ml“de 0.01 -20 gr araligindadir. In the invention, the term "flavoring agent" is used to facilitate its uptake by the patient. are expressed as substances added to the formulation. As a flavoring agent; both artificial and natural fruit essences (cherry, grape, orange, orange(s1vi), strawberry, cherry etc.), mint scent (mint sugar, menthol), coffee, cocoa, cinnamon, vanilla, artificial vanilla, Chocolate, artificial chocolate, chewing gum, peppermint or their mixtures can be used. in the find Preferably, cherry essential oil is used as flavoring agent. Aroma used in the invention The amount of donor agent is in the range of 0.01 -20 gr per gr/150ml.

Bulusta çözücü olarak; etanol, gliserin, propilen glikol, izopropil alkol, saflastirilmis su, deiyonize su veya bunlarin karisimlari kullanilabilir. Bulusta çözücü olarak tercihen etanol ve deiyonize su kullanilmaktadir. Bulusta kullanilan etanol miktari gr/1501n1“de 0.1-70 gr araligindadir. As a solvent in the invention; ethanol, glycerin, propylene glycol, isopropyl alcohol, purified water, deionized water or mixtures of these can be used. Ethanol is preferably used as the solvent in the invention. and deionized water is used. The amount of ethanol used in the invention is 0.1-70 g in gr/1501n1 is in the range.

Bulusta dagitici/baglayici inadde olarak; agar agar, kalsiyum karbonat, sodyum karbonat, aljinik asit, patates nisastasi, misir nisastasi, bugday nisastasi, prejelatinize nisasta, sodyum nisasta glikolat gibi nisastalar, mikrokristalin selüloz, çapraz-bagli polivinil pirolidon, sodyum aljinat, hidroksipropil selüloz, çapraz bagli hidroksipropil selüloz, kroskarmelloz sodyum, kil, iyon degistirici reçine, krospovidon, ksilitol, D-sorbitol, D-mannitol, laktoz, sükroz, üre, yüksek molekül agirlikli polimerler, povidon, aljinik asit, ksantan zamki, kolloidal silikon dioksit veya bunlarin karisimlari kullanilabilir. Bulusta dagitici/baglayici madde olarak tercihen prejelatinize nisasta kullanilmaktadir. Bulusta kullanilan dagitici/baglayici madde miktari %1 -45, tercihen % 10-20 agirlik oranindadir. In the invention, as a dispersive/binding substance; agar agar, calcium carbonate, sodium carbonate, alginic acid, potato starch, corn starch, wheat starch, pregelatinized starch, sodium starches such as starch glycolate, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, sodium alginate, hydroxypropyl cellulose, cross-linked hydroxypropyl cellulose, croscarmellose sodium, clay, ion exchange resin, crospovidone, xylitol, D-sorbitol, D-mannitol, lactose, sucrose, urea, high molecular weight polymers, povidone, alginic acid, xanthan gum, colloidal silicon dioxide or mixtures thereof can be used. Distributor/binder in the invention Pregelatinized starch is preferably used as a substance. used in the invention The amount of dispersant/binder is 1-45%, preferably 10-20% by weight.

Bulusta “kaydirici madde” sürtünineyi azaltan veya engelleyen bir toz karisiminin akis özelliklerini iyilestiren ajan veya ajan karisimlari olarak ifade edilmektedir. Kaydirici madde olarak; talk, kalsiyum stearat, magnezyum stearat, alüminyum stearat, polietilen glikol, tristearin, stearik asit, sodyum lauril sülfat, magnezyum laurii sülfat, kolloidal silikon dioksit, stearik asit, sodyum stearil fumarat, polioksietilen glikol, oleik asit, tripalmitil, potasyum oleat, hidrojene bitkisel yaglar, lösin, alanin, glisin, kaprilik asit, gliseril behenat, gliseril palmitostearat, sodyum benzoat, sodyum asetat, fumarik asit, çinko stearat, çinko oleat, çinko palmitat, parafinler, yag alkolleri veya bunlarin karisimlari kullanilabilir. Bulusta kaydirici madde olarak tercihen magnezyum stearat kullanilmaktadir. Bulusta kullanilan kaydirici madde miktari %0.01-15, tercihen % 0.1-1 agirlik oranindadir. The flow of a powder mixture that reduces or inhibits "lubricant" friction in the invention. It is expressed as agent or agent mixtures that improve its properties. slider as substance; talc, calcium stearate, magnesium stearate, aluminum stearate, polyethylene glycol, tristearin, stearic acid, sodium lauryl sulfate, magnesium laurii sulfate, colloidal silicon dioxide, stearic acid, sodium stearyl fumarate, polyoxyethylene glycol, oleic acid, tripalmitil, potassium oleate, hydrogenated vegetable oils, leucine, alanine, glycine, caprylic acid, glyceryl behenate, glyceryl palmitostearate, sodium benzoate, sodium acetate, fumaric acid, zinc stearate, zinc oleate, zinc palmitate, paraffins, fatty alcohols or mixtures thereof can be used. Preferably magnesium stearate as lubricant in the invention is used. The amount of lubricant used in the invention is 0.01-15%, preferably 0.1-1% is in the weight ratio.

Bulusta granülasyon sivisi olarak etanol, gliserin, propilen glikol, izopropil alkol, saflastirilmis su, deiyonize su veya bunlarin karisimlari kullanilabilir. Bulusta granülasyon sivisi olarak tercihen saIlastirilmis su kullanilmaktadir.In the invention, ethanol, glycerin, propylene glycol, isopropyl alcohol, purified water, deionized water or mixtures of these can be used. Granulation in the invention Preferably, purified water is used as the liquid.

Viskozluk bir sivinin akmaya karsi gösterdigi dirençtir. Direnç ne kadar büyükse viskozluk o denli yüksektir. Parasetamol ve/veya farrnasötik olarak kabul edilebilir türevlerini içeren oral yolla uygulamaya yönelik fannasötik surup formülasyonunun viskozite degeri 10-50 Cp, tercihen 22-32 cp araligindadir. Viscosity is the resistance of a liquid to flow. The greater the resistance, the higher the viscosity it is that high. Containing paracetamol and/or pharmaceutically acceptable derivatives Viscosity value of pharmaceutical syrup formulation for oral administration is 10-50 Cp is preferably in the range of 22-32 cp.

Mevcut bulustaki farmasötik bilesim/lerin ve/veya farmasötik olarak kabul edilebilir türevleri için uygun olan formülasyonlarina ait doz araligi; Parasetamol ve/veya farmasötik ihtiyaçlarina ve uzmanin degerlendirmesine göre ayarlanmaktadir. pharmaceutical composition(s) of the present invention and/or pharmaceutically acceptable dosage range of formulations suitable for derivatives; Paracetamol and/or pharmaceutical adjusted according to their needs and expert judgment.

Bulusta, Parasetamol ve/veya farmasötik olarak kabul edilebilir türevlerini içeren oral yolla uygulamaya yönelik farmasötik surup formülasyonu asagidakileri içermektedir (gr/150ml): - yaklasik 0.01-20 gr Parasetamol - yaklasik 0.001-10 gr bir veya daha fazla antimikrobiya] koruyucu - yaklasik 0.01-80 gr bir veya daha fazla tatlandirici madde - yaklasik 1-140 gr bir veya daha fazla sivag - yaklasik 0.001-10 gr bir veya daha fazla tamponlayici ajan - kafi miktar pH ayarlayici ajan - yaklasik 0.001-10 gr bir veya daha fazla boyar madde - yaklasik 0.01-20 gr bir veya daha fazla aroma verici ajan - yaklasik 01-70 gr bir veya daha fazla çözücü/ler ve kafi miktar çözücü/ler Parasetamol ve/veya farmasötik olarak kabul edilebilir türevlerini içeren fannasötik bilesimlerin oral uygulamasina yönelik tablet formülasyonu asagidakileri içermektedir; -yaklasik %0.1-95 agirlik oraninda Parasetamol -yaklasik %1 -45 agirlik oraninda bir veya daha fazla dagitici/baglayici madde -yaklasik %0.01-10 agirlik oraninda bir veya daha fazla koruyucu madde -yaklasik %0.01-15 agirlik oraninda bir veya daha fazla kaydirici madde -kafi miktar granülasyon sivisi Bulus esas olarak oral yolla uygulanmak üzere analjezik ve antipiretik özellikteki etken madde ve/veya farmasötik olarak kabul edilebilir türevleri ve farrnasötik olarak kabul edilebilir uygun yardimci maddeleri içeren fannasötik bilesim/lerin hazirlanmasi ile ilgilidir. Bulusun hazirlanan farmasötik bilesimlerinin surup ve tablet formunda olmasi temeldir. Böylece, Parasetamol ve/veya farrnasötik olarak kabul edilebilir türevleri uygun farmasötik formlarin sasirtici bir sekilde fiziksel ve kimyasal kararlilik açisindan oldukça stabil bir davranis sergiledigi gözlenmistir. Ayrica söz konusu surup formülasyonu ile birlikte daha kolay uygulama ve kullanim da hedeflenmistir.Oral route containing Paracetamol and/or its pharmaceutically acceptable derivatives. The pharmaceutical syrup formulation for administration contains the following (gr/150ml): - about 0.01-20 g Paracetamol - about 0.001-10 g of one or more [antimicrobial] preservatives - about 0.01-80 g of one or more sweetening agents - about 1-140 g one or more sivag - about 0.001-10 g of one or more buffering agents - sufficient amount of pH adjusting agent - approximately 0.001-10 g of one or more dyestuffs - about 0.01-20 g of one or more flavoring agents - approximately 01-70 g of one or more solvent(s) and sufficient amount of solvent(s) Pharmaceuticals containing paracetamol and/or its pharmaceutically acceptable derivatives The tablet formulation for oral administration of the compositions comprises: -approximately 0.1-95% by weight Paracetamol -approximately 1% to 45% by weight of one or more dispersing/binding agents -approximately 0.01-10% by weight of one or more preservatives -one or more lubricants at a rate of approximately 0.01-15% by weight -sufficient amount of granulation fluid The invention is mainly intended for oral administration as an agent with analgesic and antipyretic properties. substance and/or pharmaceutically acceptable derivatives and pharmaceutically acceptable derivatives by the preparation of pharmaceutical composition(s) containing suitable excipients is relevant. Pharmaceutical compositions of the invention in syrup and tablet form is fundamental. Thus, Paracetamol and/or pharmaceutically acceptable derivatives are suitable. Surprisingly, pharmaceutical forms are quite high in terms of physical and chemical stability. A stable behavior was observed. In addition, with the said syrup formulation Easier application and use are also targeted.

Bulusun özellikleri asagidakilerle sinirli kalmamak üzere örnekler asagida verilmistir: Parasetamol ve/veya farmasötik olarak kabul edilebilir türevlerini içeren oral yolla uygulamaya yönelik farmasötik surup formülasyonu asagidakileri içermektedir(g/150ml): - yaklasik 0.01-20 gr Parasetamol - yaklasik 0.01-10 gr sodyum metil paraben, sodyuin propil paraben ve potasyum sorbat - yaklasik 0.01-80 gr sukroz ve sodyum sakkarin dihidrat - yaklasik 1-140 gr gliserol ve propilen glikol - yaklasik 0.001-10 gr sitrik asit anhidrus ve sodyum sitrat dihidrat - kafi miktar sitrik asit monohidrat - yaklasik 0.001-10 gr kirmizi gida boyasi (food red & ponceu 4R) - yaklasik 0.01-20 gr visne esansi - yaklasik (11-70 gr etanol ve kafi miktar deiyonize su Parasetamol ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesimlerin oral uygulamasina yönelik tablet formülasyonu asagidakileri içermektedir; -yaklasik %O.1-95 agirlik oraninda Parasetamol -yaklasik %1 -45 agirlik oraninda prejelatinize nisasta -yaklasik %0.01-10 agirlik oraninda potasyum sorbat -yaklasik %0.01-15 agirlik oraninda magnezyum stearat Parasetamol ve/veya fannasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesimlerin oral uygulamasina yönelik tablet forrnülasyonu asagidakileri içermektedir; -yaklasik 1-250mg prejelatinize nisasta -yaklasik 0.01 -20m g potasyum sorbat -yaklasik 0.01 -25m g magnezyum stearat Üretim prosesi 1: Hammaddeler üretim formülüne uygun tartilir. Imalat kazanina alinan belirli miktardaki deiyonize su uygun sicaklikta isitilir ve Sukroz eklenip belirli bir süre karistirilir. Çözeltiye Gliserol ve Propilen Glikol eklenerek belirli bir süre karistirilir. Imalat kazani uygun sicakliga sogutulur. Sodyum sakkarin dihidrat, sodyum sitrat dihidrat ve sitrik asit anhidrus çözeltiye eklenerek belirli bir süre karistirilir. Çözeltiye Parasetamol eklenerek belirli bir süre karistirilir. Baska bir kazana etanol alinir ve Sodyum metil paraben, sodyum propil paraben ve potasyum sorbat eklenerek karistirilir. Ethanol çözeltisine visne esansi ve Food Red & Ponceau 4R eklenerek belirli bir süre karistirilir. Etanol çözeltisi imalat kazanindaki çözeltiye aktarilarak belirli bir süre karistirilir. Çözeltinin pH”i kontrol edilir ve gerektigi takdirde belirli bir miktar Sitrik asit çözeltisi ile istenen pH°ya getirilir. Çözeti hacmine deiyonize su ile tamamlanir ve belirli bir süre karistirilir.Ürün uygun araliktaki filtrelerden ön filtre ve final filtre olarak sirasiyla süzülür. Hazirlanan çözelti amber renkli cam siselere Üretim prosesi 2: Parasetamol ve Prejelatinize Nisasta uygun araliktaki elekten eleiiirler. Parasetamol ve Prejelatinize Nisasta, uygun hizda belirli bir süre granülasyon kazani içerisinde karistirilir. Üretim formülüne uygun miktarda saflastirilmis su tartilir. Potasyum Sorbat karistirici içerisinde karismakta olan suya yavasça eklenir. Berrak bir çözelti olusana kadar karisima devam edilir. Granülasyon sivisi belirli bir süre içerisinde uygun hizda toz karisima ilave edilir. Düzgün granüllerin olustugu kirici açilarak yeterli bir süre boyunca karistirici ile beraber çalistirildiktan sonra kontrol edilir. Granülasyonun yeterliligi kontrol edilir.Examples of the features of the invention are given below, but not limited to the following: Oral route containing paracetamol and/or its pharmaceutically acceptable derivatives Pharmaceutical syrup formulation for administration contains (g/150ml): - about 0.01-20 g Paracetamol - approximately 0.01-10 g of sodium methyl paraben, sodium propyl paraben and potassium sorbate - about 0.01-80 g of sucrose and sodium saccharine dihydrate - about 1-140 g of glycerol and propylene glycol - approx. 0.001-10 g of citric acid anhydrous and sodium citrate dihydrate - sufficient amount of citric acid monohydrate - approximately 0.001-10 gr red food coloring (food red & ponceu 4R) - approx. 0.01-20 g of cherry essential oil - approx. (11-70 g ethanol and enough deionized water Pharmaceutical containing paracetamol and/or its pharmaceutically acceptable derivatives The tablet formulation for oral administration of the compositions comprises: -approximately 0.1-95% by weight Paracetamol -approximately 1% to 45% by weight of pregelatinized starch -approximately 0.01-10% by weight potassium sorbate -approximately 0.01-15% by weight magnesium stearate Pharmaceutical containing paracetamol and/or pharmaceutically acceptable derivatives Tablet formulation for oral administration of the compositions includes: -approximately 1-250mg pregelatinized starch -approximately 0.01 -20mg potassium sorbate -approximately 0.01 -25mg magnesium stearate Production process 1: Raw materials are weighed according to the production formula. A certain amount taken into the manufacturing boiler Deionized water is heated at the appropriate temperature and Sucrose is added and mixed for a certain time. to the solution Glycerol and Propylene Glycol are added and mixed for a certain time. Suitable for manufacturing boiler cooled to temperature. Sodium saccharine dihydrate, sodium citrate dihydrate and citric acid anhydrous It is added to the solution and mixed for a certain time. By adding Paracetamol to the solution, a certain time is mixed. Ethanol is taken into another boiler and Sodium methyl paraben, sodium propyl Paraben and potassium sorbate are added and mixed. Vinegar essence and Food to ethanol solution Red & Ponceau 4R is added and mixed for a certain time. Ethanol solution in the manufacturing vessel transferred to the solution and mixed for a certain time. The pH of the solution is checked and Otherwise, it is brought to the desired pH with a certain amount of citric acid solution. To the volume of the solution It is completed with deionized water and mixed for a certain period of time. The product is filtered from the appropriate range. filtered as a pre-filter and a final filter, respectively. The prepared solution is poured into amber colored glass bottles. Production process 2: Paracetamol and Pregelatinized Starch are sifted through a suitable range of sieves. Paracetamol and Pregelatinized Starch is mixed at the appropriate speed for a certain period of time in the granulation vessel. The amount of purified water in accordance with the production formula is weighed. Potassium Sorbate mixer It is slowly added to the water that is mixed in it. Mix until a clear solution is formed. continues. Granulation liquid is added to the powder mixture at the appropriate speed within a certain time. is done. The crusher, which forms smooth granules, is opened and mixed with the mixer for a sufficient time. controlled after working together. The adequacy of the granulation is checked.

Gerekirse bir miktar daha saflastirilmis su ilave edilebilir. Granülasyon sonrasi elde edilen yas graiiül akiskan yatakli kurutucuya aktarilarak uygun sicaklikta, istenilen nem araligi saglanaiia kadar kurutulur. Kurutulan granüller uygun araliktaki elekten elenir ve karisitiriciya aktarilir. Karisim belirli bir süre uygun hizda karistirilir. Magnezyum Stearat uygun araliktaki elekten elendikten sonra karistiricidaki karisim üzerine ilave edilir ve belirli bir süre uygun hizda karistiricida karistirilir. Toz karisim tablet zimbasi ile uygun fiziksel özellikte tabletler basilir.If necessary, some more purified water can be added. Obtained after granulation The wet grain is transferred to the fluidized bed dryer at the appropriate temperature and the desired humidity range. It is dried until it sags. The dried granules are sieved through a suitable sieve and transferred to the mixer. The mixture is mixed at the appropriate speed for a certain time. Magnesium Stearate After sifting through the appropriate sieve, it is added to the mixture in the mixer and It is mixed in the mixer at the appropriate speed for a certain period of time. Suitable with powder mix tablet punch tablets with physical properties are printed.

Claims

REQUESTS . Preparation of pharmaceutical composition(s) containing an analgesic and antipyretic active ingredient and/or its pharmaceutically acceptable derivatives and suitable pharmaceutically acceptable excipients for oral use. . It is a pharmaceutical composition/s as in claim 1 and its feature is; The analgesic and/or antipyretic active ingredient is acetylsalicylic acid, aloxiprine, choline salicylate, sodium salicylate, salicyl salsalate, ethenzamide, morpholine salicylate, dipyrocetyl, benorilate, diflunisal, potassium salicylate, guacetysal, carbasalate calcium, imidazole, metanasylate, phenazole, propyphenazone, nifenazone, paracetamol, phenacetin, busetin, propacetamol, rimazolium, glafenin, floctafenin, viminol, nefopam, flupirtine, ziconotide, methoxyflurane, nabiximols, morphine, opium, hydromorphone, nicomorphine, morphodiabene, nicomorphine, diacodone, nicomorphine, diacodone, nicomorphine, diacocin fentanyl, dextromoramide, pyrithramide, dextropropoxyphene, bezitrantiide, pentazocine, phenazosine, buprenorphine, butorphanol, nalbuphine, tilidine, traniadol, dezosine, nieptazinol, taperitadol, dihydroergotamine, ergotamiii, metisergidine, drolysuristriptyphane, narcissius, triptytanzine, narcissius eletriptan, frovatriptan, pizotifen, clonidine, iprazochrome, dimethothiazine, oxeto Ron is selected from among zucapsaicin and/or pharmaceutically acceptable derivatives. . It is a pharmaceutical composition/s as in Claim 2 and its feature is; The active ingredient with analgesic and/or antipyretic properties is preferably Paracetamol and/or pharmaceutically acceptable derivatives. . Pharmaceutical syrup formulation for oral administration containing paracetamol and/or its pharmaceutically acceptable derivatives contains - approximately 0.01-20 g Paracetamol - approximately 0.001-10 g one or more antimicrobial preservatives - approximately 0.01-80 g one or more sweeteners - about 1-140 g of one or more coatings - about 0.001-10 grams of one or more buffering agents - enough amount of pH adjusting agents - about 0.001-10 grams of one or more dyestuffs - about 0.01-20 grams of one or more excess flavoring agent - approximately 01-70 g of one or more solvents and sufficient amount of solvent. Pharmaceutical syrup formulation for oral administration containing paracetamol and/or its pharmaceutically acceptable derivatives contains - approx. 0.0] -20 g Paracetamol - approx. 0.001-10 g sodium methyl paraben, sodium propyl paraben and potassium sorbate - approx. 0.01-80 g sucrose and sodium saccharine dihydrate - approx. 1-140 g glycerol and propylene glycol - approx. 0.001-10 g citric acid anhydrous and sodium citrate dihydrate - enough citric acid monohydrate - approx. 0.001-10 g red food coloring (food red & ponceu 4R) - approx. 0.01-20 gr. sour cherry essence - approx. 01-70 gr. ethanol and sufficient amount of deionized water. Tablet formulation for oral administration of pharmaceutical compositions containing paracetamol and/or its pharmaceutically acceptable derivatives contains the following; -about 0%. 1-95 wt% Paracetamol -approximately 1-15% by weight one or more dispersing/binding agents -approximately 001-10% by weight one or more preservatives -approximately 001-15% by weight one or more lubricants - sufficient amount of granulation fluid. Tablet formulation for oral administration of pharmaceutical compositions containing paracetamol and/or its pharmaceutically acceptable derivatives includes; - about 0.1-95% by weight of Paracetamol - about 1% to 45% by weight of pregelatinized starch - about 0.01-10% by weight of potassium sorbate - about 0.01-15% by weight of magnesium stearate. It is a pharmaceutical composition/s as in Claims 4 and 6 and its feature is; antimicrobial preservative; parabens such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, sodium benzoate, potassium sorbate, sodium methyl paraben, sodium propyl paraben, edetatin salts (salts of EDTA such as ethylenediaminetetracetic acid or disodium edetate), glycerine, or benzalkonium chloride is chosen from among the mixtures. It is a pharmaceutical composition/s as in Claim 87 and its feature is; The antimicrobial preservative used in the syrup formulation is preferably sodium methyl paraben and sodium propyl paraben, preferably potassium sorbate as the antimicrobial preservative synergist, and the preservative used in the tablet formulation of the invention is preferably potassium sorbate. It is a pharmaceutical composition/s as in Claim 4 and its feature is; flavoring agent; sugar, glycerin, molasses, fructose, sucralose, sucrose, potassium acesulfame, sodium saccharin, sodium saccharine dihydrate, mannitol, aspartame, sodium cyclamate, sorbitol or their mixtures. It is a pharmaceutical composition/s as in Claim 10 and its feature is; the sweetener is preferably sucrose and sodium saccharine dihydrate. It is a pharmaceutical composition/s as in Claim 4 and its feature is; macrogol derivatives of plaster, petrolatum, wax modified vaseline, liquid petrolatum, white petrolatum, lanolin or lanolin derivatives, vegetable oils such as castor oil, coconut oil, olive oil, cottonseed oil, polyethylene glycol, paraffin, anhydrous, white soft paraffin, glycerol, propylene glycol or their mixtures. It is a pharmaceutical composition/s as in claim 12 and its feature is; The plaster is preferably glycerol and propylene glycol. It is a pharmaceutical composition/s as in Claim 4 and its feature is; buffering agent; mono sodium citrate, citric acid, citric acid anhydrous, sodium citrate dihydrate, sodium chloride, citric acid monohydrate, sodium hydrogen carbonate (sodium bicarbonate), sodium carbonate, sodium glycine carbonate, potassium carbonate, potassium bicarbonate or mixtures thereof. It is a pharmaceutical composition/s as in claim 14, and its feature is that the buffering agent is preferably citric acid anhydrous and sodium citrate dihydrate. It is a pharmaceutical composition/s as in claim 4, and its feature is that the pH adjusting agent is hydrochloric acid, sodium hydroxide, sodium carboiate, sodium bicarbonate, sodium silicate, disodium orthophosphate, calcium carbonate, magnesium carbonate, magnesium hydroxide, magnesium aluminate, diethanol amine, sodium alginate, ethylenediamine, meglumine, mono sodium citrate, citric acid, citric acid monohydrate, sodium citrate dihydrate or mixtures thereof. They are pharmaceutical composition(s) as in Claim 15, and their feature is that the pH adjusting agent is citric acid monohydrate. They are pharmaceutical compositions as in Claim 4, and its feature is that the dyestuff is iron oxide pigments such as iron oxide, red iron oxide, ß-carotene, red beet powder, chlorophyll, tartrazine, yellow orange, quinoline yellow, erythrosine, titanium dioxide, caramel, red food coloring (food red & p onceu 4R) or their mixtures. Istein is pharmaceutical composition/s as in 18°. Its feature is; the dyestuff is preferably red food dye (food red & ponceu 4R). It is a pharmaceutical composition/s as in Claim 4 and its feature is; flavoring agent; both artificial and natural fruit essences (cherry, grape, orange, orange (liquid), strawberry, sour cherry etc.), mint scent (mint sugar, menthol), coffee, cocoa, cinnamon, vanilla, artificial vanilla, chocolate, artificial chocolate, gum , peppermint or a mixture of these. It is a pharmaceutical composition/s as in Claim 20 and its feature is; The flavoring agent is preferably cherry essential oil. It is a pharmaceutical composition/s as in Claim 4 and its feature is; the solvent; ethanol, glycerin, propylene glycol, isopropyl alcohol, purified water, deionized water or their mixtures. It is a pharmaceutical composition/s as in request 22. Its feature is; the solvent is preferably ethanol and deionized water. It is pharmaceutical composition/s as in claim 6 and its feature is; as a dispersing/binding agent; Starches such as agar agar, calcium carbonate, sodium carbonate, alginic acid, potato starch, corn starch, wheat starch, pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, cross-linked polyvinyl pyrrolidone, cross-linked polyvinyl pyrrolidone, sodium alginate, hydroxypropyl hydroxycellulose, hydroxypropyl cellulose, croscannellose sodium, clay, ion exchange resin, crospovidone, xylitol, D-sorbitol, D-mannitol, lactose, sucrose, urea, high molecular weight polymers, povidone, alginic acid, xanthan zainki, colloidal silicon dioxide or a selection of mixtures thereof. It is a pharmaceutical composition/s as in Claim 247 and its feature is; The dispersant/binding agent is preferably pregelatinized starch. It is a pharmaceutical composition/s as in Claim 6 and its feature is; lubricant; talc, calcium stearate, magnesium stearate, aluminum stearate, polyethylene glycol, tristearin, stearic acid, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silicon dioxide, stearic acid, sodium stearyl fumarate, polyoxyethylene glycol, oleic acid, tripalmityl, potassium oleate, hydrogenated vegetable oils, leucine, alanine, glycine, caprylic acid, glyceryl behenate, glyceryl palmitostearate, sodium benzoate, sodium acetate, fumaric acid, zinc stearate, zinc oleate, zinc palmitate, paraffins, fatty alcohols or mixtures thereof. It is a pharmaceutical composition/s as in Claim 26 and its feature is; preferably the lubricant is magnesium stearate. It is pharmaceutical composition/s as in Claim 67 and its feature is; granulation fluid is selected from ethanol, glycerin, propylene glycol, isopropyl alcohol, purified water, deionized water or mixtures thereof. It is pharmaceutical composition/s as in claim 28 and its feature is; the granulation liquid is preferably purified water. It is a pharmaceutical composition/s according to any of the above claims and its feature is; the dose range of the formulations of the active substance suitable for pharmaceutical compositions; 10-1ZOOmg for paracetamol and/or its pharmaceutically acceptable derivatives. It is a pharmaceutical composition/s according to any of the above claims and its feature is; pain (mild, moderate, severe), arthralgia, fever, headache, migraine, dysmenorrhea, toothache, tooth pulling pain, sore throat, musculoskeletal pain, menstrual pain, osteoarthritis, neuralgia, influenza, fever, and fever symptomatic relief in colds, in the treatment of many bacterial and viral infections such as bronchitis, pharyngitis, tracheal bronchitis, sinusitis, pneumonia, middle ear inflammation, cervical adenitis, in the treatment of tonsillitis (tonsilitis), postimmunization (post-vaccination) reactions and/or prophylactic and/or is indicated for therapeutic treatment.