Priprava i evaluacija mukoadhezivnih filmova glipizida

Glipizide is mainly absorbed in the proximal areas of the gastrointestinal tract. The purpose of this study was formulation and evaluation of mucoadhesive films to prolong the stay of drug in its absorption area. Glipizide was formulated in a mucoadhesive film that could be retained in the stomach for prolonged time intervals. Polymeric films were designed with various compositions of hydroxypropyl cellulose and polyethylene glycol 400 (PEG 400). Properties of the mucoadhesive film such as tensile strength, percentage elongation, swelling index, moisture content, pH and viscosity of polymeric dispersion, film thickness, drug concentration, uniformity and mucoadhesion in a simulated gastric environment were evaluated. In addition, percentage drug retained in stomach mucosa was estimated using a simulated dynamic stomach system as a function of time. Increase in hydroxypropyl cellulose concentration resulted in a higher tensile strength and elongation at break, while increase in concentration of PEG 400 was reflected in a decrease of tensile strength and increase of elongation at break. Glipizide/hydroxypropyl cellulose/PEG 400 (2.5:1:0.5) (GF5) was found to be the optimal composition for a novel mucoadhesive stomach formulation that showed good peelability, relatively high swelling index, moderate tensile strength, and stayed on rat stomach mucosa up to 8 h. In vivo testing of the mucoadhesive films with glipizide demonstrated a potential hypoglycemic effect.Glipizid se pretežno apsorbira u proksimalnom dijelu gastrointestinalnog trakta. Cilj rada je priprava i evaluacija mukoadhezivnih filmova s kojima bi se produljilo zadržavanje lijeka u predjelu apsorpcije. Pripravljeni su mukoadhezivni filmovi glipizida koji se produljeno zadržavaju u želucu. Polimerni filmovi sadržavali su različite količine hidroksipropil celuloze i polietilen glikola 400 (PEG 400). Evaluirana su sljedeća svojstva mukoadhezivnih filmova: čvrstoća, postotak elongacije, indeks bubrenja, sadržaj vlage, pH i viskoznost polimerne disperzije, debljina filma, koncentracija lijeka, jednolikost i mukoadhezivnost u simuliranom želučanom soku. Na dinamičkom modelu želuca određivan je i postotak lijeka koji se zadržava u sluznici želuca u ovisnosti o vremenu. Povećanjem koncentracije hidroksipropil celuloze povećavaju se čvrstoća i elongacija, dok se povećanje koncentracije PEG 400 reflektira na smanjenje čvrstoće i povećanje elongacije kod loma. Omjer glipizid/hidroksipropil celuloza/PEG 400 (2,5:1:0,5) (GF5) bio je optimalan za pripravu mukoadhezivnih formulacija, s dobrom kalavošću, relativno visokim indeksom bubrenja, umjerenom čvrstoćom te zadržavanjem u sluznici želuca štakora do 8 h. U in vivo testiranjima mukoadhesivni filmovi s glipizidom pokazali su potencijalni hipoglikemijski učinak

Gastroretentive drug delivery system of ranitidine hydrochloride: Formulation and in vitro evaluation

The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 32 full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous (X1) and stearic acid (X2) were selected as independent variables. The times required for 50% (t50) and 80% drug dissolution (t80), and the similarity factor f2 were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity factor f2 was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2=75) among all the batches, and this similarity is also reflected in t50 (∼214 minutes) and t80 (∼537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate retardant can produce a drug dissolution profile similar to a theoretical dissolution profile