Topikalni pripravci za liječenje analne fisure

professional thesis

• Author: Maja Kišan
• Mentor: Željka Vanić (mentor)
• Committee member: Ivana Perković (predsjednik povjerenstva)
• Committee member: Željka Vanić (član povjerenstva)
• Committee member: Marijana Erceg (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2018-06-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj istraživanja
Trenutno na hrvatskom tržištu ne postoje registrirani topikalni pripravci za liječenje analne fisure, već se terapija provodi magistralnim pripravkom diltiazemklorida koji se izrađuje u obliku komercijalno dostupnog gela hidroksietilceluloze.
Svrha ovog rada bila je evaluacija postojećeg magistralnog pripravka i razvoj inovativne podloge za uklapanje diltiazemklorida – kitozanskog hidrogela. Provedena su in vitro ispitivanja oslobađanja diltiazemklorida iz hidroksietilceluloznog i kitozanskog hidrogela te detaljna reološka karakterizacija postojećeg i inovativnog magistralnog pripravka.
Materijali i metode
Hidroksietilceluloznom i kitozanskom gelu je izmjeren pH, podešen na pH5,5, te ispitan utjecaj pH gela na njegova reološka svojstva i profil oslobađanja diltiazemklorida. In vitro ispitivanja oslobađanja diltiazemklorida iz svih hidrogelova provedena su korištenjem Franz difuzijske ćelije. Reološka ispitivanja uključivala su određivanje profila viskoznosti, testove promjene frekvencije, amplitude, oporavka strukture i adhezivnosti.
Rezultati
Provedenim istraživanjima i usporedbom rezultata dobivenim s oba tipa hidrogela pokazano je da sastav podloge, tj. tip hidrogela i njegova pH vrijednost utječu na
oslobađanje lijeka i reološka svojstva pripravka. Brzina oslobađanja diltiazemklorida iz oba tipa hidrogela (hidroksietilceluloznog i kitozanskog) je bila u obrnuto proporcionalnom odnosu s viskoznosti hidrogelova. Najbrže oslobađanje diltiazemklorida postignuto je iz izvornog hidroksietilceluloznog gela (pH 4,5), dok se korištenjem kitozanskog hidrogela oslobađanje lijeka usporava, pogotovo iz gela više pH vrijednosti (pH 5,5). Provedeni oscilacijski testovi potvrdili su razlike između hidrogelova. Hidroksietilcelulozni gelovi su imali više izražena viskozna nego elastična svojstva te širi raspon linearnog viskoelastičnog područja, dok je kod kitozanskih gelova modul pohrane G' bio veći od modula gubitka G''.
Zaključak
Budući da se kitozanskim hidrogelom (pH5,5) postiže sporije oslobađanje diltiazemklorida, te imajući u vidu potencijalni antimikrobni učinak i povoljno djelovanje kitozana na zacjeljivanje rana, mišljenje je da bi takav pripravak bio prikladan za lokalnu terapiju analne fisure. Stoga je neophodno provesti daljnja ispitivanja kojima bi se potvrdila djelotvornost inovativnog pripravka.

Abstract (english)

Objectives
Currently there are no commercially available topical formulations for the therapy of anal fissure on the Croatian market, and extemporaneously compounded medications are made by incorporating diltiazem hydrochloride in hydroxyethylcellulose gel base. Therefore, the main objective of this study was an evaluation of the aforementioned medication and development of innovative topical formulation based on chitosan hydrogel. All the formulations were assessed for the drug release and rheological properties.
Material and Methods
Hydroxyethylcellulose and chitosan hydrogels were assessed for their pH values, adjusted to achieve gel pH5.5, and the effect of the gel pH on the drug release profile was examined. In vitro release of diltiazem hydrochloride from all the hydrogels was performed by Franz diffusion cell method. In addition, all the hydrogels were rheologically characterized including viscosity, adhesion and structure recovery investigations, as well as amplitude and frequency sweep testing.
Results
The vehicle composition, i.e. type of the hydrogel and its pH value, affected the drug release profile and rheological properties. The release rate of diltiazem hydrochloride from the both types of hydrogels (hydroxyethylcellulose and chitosan) was inversely
proportional to the hydrogel viscosity. The fastest release of the drug was achieved from hydroxyethylcellulose gel (pH 4.5), while the release from chitosan hydrogel was slowed down, especially at higher pH (pH 5.5). The oscillation tests confirmed the differences between the examined hydrogels. Hydroxyethylcellulose gels exhibited more pronounced viscous than elastic properties and a wider range of linear viscoelastic area, while chitosan gel demonstrated greater storage modulus G’ than the loss modulus G’’.
Conclusion
Taking into account sustained release of the drug from chitosan hydrogel (pH5.5) and potential antimicrobial and wound healing activities of chitosan, it can be assumed that the chitosan-based formulation could be more suitable for the topical treatment of anal fissure. Therefore, further investigations should be carried out to confirm the efficacy of the innovative formulation.

• Keywords: topikalna primjena lijeka; analna fisura; hidroksietilceluloza; kitozanski hidrogel; kitozan; magistralni pripravci
• Keywords (english): topical application of the drug; anal fissure; hydroxyethylcellulose; chitosan gel; chitosan; compounded medications
• Language: croatian
• URN:NBN: urn:nbn:hr:163:313757
• Study programme: Title: Dermopharmacy and cosmetology; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni magistar/sveučilišna magistra dermofarmacije i kozmetologije (sveučilišni magistar/sveučilišna magistra dermofarmacije i kozmetologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-21 09:57:17