Proučevanje očesnih vložkov timolola in nepafenaka, izdelanih iz različnih polimerov

Topler, Eva (author), Planinšek, Odon (mentor)

Očesni vložki so opredeljeni kot sterilni, tanki, z učinkovino impregnirani trdni ali poltrdni pripomočki, ki se namestijo v veznico ali konjunktivno vrečko in so posebej oblikovani glede na velikost in obliko za oftalmološko uporabo. Sestavljeni so iz polimernega matriksa, ki je impregniran z zdravilno učinkovino (ZU). Namen magisterske naloge je razviti očesne vložke z različnimi lastnostmi, vključno z različnimi ZU in polimeri. Raziskovani parametri so bili topnost ZU, vsebnost učinkovine v formulaciji in vrsta polimera. Preiskovali smo sproščanje ZU, nabrekanje, erozijo in razpad vložkov. Pripravili smo dvanajst različnih očesnih vložkov z uporabo dveh različnih ZU in sicer timolol hidrogen maleata (TIM) in nepafenaka (NEP), ter štirih različnih polimerov. Vložke s TIM smo dodatno pripravili pri dveh različnih koncentracijah 5% in 20%. TIM je neselektivni beta-adrenergični antagonist, s topnostjo 5 mg/mL, kar velja za dobro topno učinkovino. To je glavna razlika glede na NEP, katerega topnost znaša 0,02 mg/mL. NEP je oftalmološko nesteroidno protivnetno zdravilo. ZU smo homogeno zmešali z različnimi polimeri. Uporabili smo dva hidrofilna polimera, hidroksipropilmetil celuloza (HPMC) K100LV in HPMC K4M, ter dva lipofilna polimera, Kollidon SR in ETOCEL 10, da bi pridobili različne profile sproščanja. Vsak očesni vložek je vseboval eno ZU v kombinaciji z enim polimerom. Študije razpadnosti so pokazale hitrejši razpad vložkov, ki so vsebovali hidrofilne polimere. Primerjava med HPMC K4M in K100LV je pokazala, da je nižja molekulska masa pokazala krajši čas razpadnosti vložkov. To je bilo v skladu s študijami sproščanja, kjer je nižja molekulska masa pokazala hitrejše sproščanje. Tudi nabrekanje in erozija sta bila višja pri hidrofilnih polimerih. Študije sproščanja so pokazale hitrejše sproščanje pri 20% koncentraciji zdravila pri uporabi hidrofilnega polimera. 5% TIM je pokazal hitrejše sproščanje kot 5% NEP, kar je bilo pričakovano glede na nižjo topnost NEP.

• Language: Slovenian
• Keywords: oko, očesna bolezen, oftalmični vložki, timololni hidrogen maleat, nepafenac, hidroksipropil metilceluloza, Kollidon SR, Etocel 10, razpad, raztapljanje, nabrekovanje, erozija.
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2024
• PID: 20.500.12556/RUL-158520
• Publication date in RUL: 14.06.2024

Secondary language

• Language: English
• Title: Analysis of ophthalmic inserts Timolol and Nepafenac with different polymers

Abstract

Ocular inserts are defined as sterile, thin, drug-impregnated, solid or semisolid devices placed into the cul-de-sac or conjunctival sac, whose size and shape are specially designed for ophthalmic application. They contain polymeric support that may or may not contain a drug. The aim of this work was to develop ocular inserts with various characteristics, including different active pharmaceutical ingredients (API) and polymers. The parameters investigated were API solubility, drug loading, polymer type and molecular weight. Those systems were characterized in terms of release, swelling, erosion and disintegration. Twelve different ocular inserts were prepared using two different APIs, timolol hydrogen maleate (TIM) and nepafenac (NEP), as well as four different polymers. TIM insert were additionally prepared at two drug loadings, 5% and 20%. TIM hydrogen maleate is a nonselective beta-adrenergic antagonist, which is given in an eye drop solution to reduce intraocular pressure and is an effective agent for glaucoma and hypertension. The drug is highly water soluble (5 mg/mL), which is the main difference from the second API under investigation NEP, whose water solubility is 0,02 mg/mL. NEP is an ophthalmic non-steroidal anti-inflammatory drug, used for the symptomatic treatment of pain and inflammation associated with cataract surgery. Two hydrophilic polymers HPMC K100LV and HPMC K4M and two lipophilic polymers Kollidon SR and ETHOCEL 10 were used to gain different release profiles. Each ocular insert contained one API in combination with one polymer. Disintegration studies showed faster disintegration for hydrophilic polymers. Comparing HPMC K4M and K100LV, the lower molecular weight polymer showed the shortest disintegration time. This was in accordance with release studies, where the lower molecular weight polymer showed the fastest release. Also swelling and erosion were higher for hydrophilic polymers. Higher swelling was seen in HPMC K4M than in HPMC K100 LV. Release studies showed a faster release for 20% drug loading when using a hydrophilic polymer. 5% TIM showed quicker release than 5% NEP, which was expected based on the lower water solubility of NEP.

• Keywords: eye, eye diseases, ophthalmic inserts, timolol hydrogen maleate, nepafenac, Hydroxypropyl Methylcellulose, Kollidon SR, Etocel 10, disintegration, dissolution, swelling, erosion.