Vpliv hipromeloze kot veziva na pretvorbo tekočega samo-mikroemulgirajočega sistema v trdno farmacevtsko obliko z vlažnim granuliranjem

Šmigoc, Matic (author), Zvonar Pobirk, Alenka (mentor), German Ilić, Ilija (co-mentor)

Peroralna pot aplikacije zdravil je zaradi preprostosti, dobrega sodelovanja bolnikov ter odsotnosti zapletov, ki so prisotni pri drugih poteh, še vedno najbolj priljubljena. Ker je večina novoodkritih zdravilnih učinkovin slabo vodotopnih, peroralna aplikacija ni vedno mogoča. Eden izmed pristopov za izboljšanje topnosti in posledično biološke uporabnosti so na lipidih osnovani sistemi, med katerimi so vedno bolj priljubljeni samo-mikroemulgirajoči sistemi (SMES). Ti sistemi imajo v primerjavi z drugimi na lipidih osnovanih sistemih boljšo stabilnost, obenem pa imajo večji vpliv na izboljšanje biološke uporabnosti. Namen našega dela je bil proučiti vpliv hipromeloze kot veziva na pretvorbo tekočega SMES v trdno farmacevtsko obliko z metodo vlažnega granuliranja. Kot veziva pri vlažnem granuliranju smo uporabljali hipromeloze Pharmacoat® 603, Pharmacoat® 615 in MethocelTM K100 Premium LV, kot mezoporozni nosilec Syloid® 244 FP, kot modelno učinkovino pa karvedilol. Končni cilj je bil izdelana zrnca SMES stisniti v tablete ustreznih lastnosti in pri tem ohraniti sposobnost tvorjenja mikroemulzije. Pri preliminarnem ročnem granuliranju smo ugotovili, da vrsta in delež veziva ne vplivata na pretočne lastnosti izdelanih zrnc SMES. Z DSC analizo smo ugotovili, da v naših formulacijah ni prisotnih ostankov kristaliničnega karvedilola. Ker se pri in vitro preskusu sproščanja, pri uporabi veziva MethocelTM K100 Premium LV, modelna učinkovina ni sprostila v celoti, smo delo nadaljevali le z vezivoma Pharmacoat®. Na hitrovrtečem granulatorju smo izdelali zrnca z 1,85 % in s 7,45 % Pharmacoat® 603 in 615, ki smo jih stisnili v tablete ustreznih mehanskih in ohranjenih samo-mikroemulgirajočih lastnosti. Večji delež dodane hipromeloze kot veziva je ugodno vplival na hitrost sproščanja učinkovine. Učinkovina se je najhitreje sproščala iz tablet, izdelanih iz zrnc s 7,45 % Pharmacoat® 603. V celoti pa se je sprostila le iz tablet, izdelanih iz zrnc s 1,85 % veziva Pharmacoat® 615.

• Language: Slovenian
• Keywords: vlažno granuliranje, karvedilol, hipromeloza, samo-mikroemulgirajoči sistemi (SMES), trdni samo-mikroemulgirajoči sistemi
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2022
• PID: 20.500.12556/RUL-143403
• Publication date in RUL: 20.12.2022

Secondary language

• Language: English
• Title: Influence of hypromellose binders on transformation of liquid self-microemulsifying system into a solid dosage form by wet granulation method

Abstract

Oral drug administration is one of the most popular drug administration pathways, because of its simplicity, good patient compliance and the absence of adverse effects associated with other drug delivery pathways. Most of newly-discovered API's are poorly water-soluble, which means that oral drug administration is not always possible. One of the approaches to improving water-solubility and the bioavailability of API's is the use of lipid based drug delivery systems, out of which self-microemulsifying drug delivery systems (SMEDDS) are becoming increasingly more popular. These systems have better stability and further improve bioavailability. The purpose of our work was to study the effect of hypromellose binders on the transformation of liquid SMEDDS into solid dosage form by wet granulation method. For the wet granulation we used hypromelloses Pharmacoat® 603, Pharmacoat® 615 and MethocelTM K100 Premium LV as binders, Syloid® 244 FP as the carrier and carvedilol as the model API. The goal was to produce tablets with adequate properties from manufactured granules, while preserving their ability to form microemulsions. During preliminary manual granulation, we discovered that type and concentration of the binder does not have an effect on the flow properties of produced granules. We established that no crystalline carvedilol was present using DSC. During the in vitro dissolution test, the only granules that did not release all of the model API, were produced with MethocelTM K100 Premium LV, resulting in our continuing using only the Pharmacoat® binders. Using high-shear granulation we produced granules with 1,85 % and 7,45 % of binders Pharmacoat®, from which we produced tablets with adequate mechanical properties that retained their self-microemulsifying ability. A higher percentage of added hypromellose had a positive effect on the speed of liberation of the API. The API liberated fastest from tablets produced with granules with 7,45 % Pharmacoat® 603. The only tablets from which the API liberated in its entirety were produced from granules with 1,85 % Pharmacoat® 615.

• Keywords: wet granulation, carvedilol, hypromellose, self-microemulsifying drug delivery systems (SMEDDS), solid self-microemulsifying drug delivery systems (sSMEDDS)