Development and Characterization of a Fixed-Dose Orodispersible Film of Telmisartan and Indapamide for Enhancing Dissolution

Authors : Dilara Örgül, Aslı Yigit, Yakup Gültekin, Sema Arısoy

Pages : 513-530

Doi:10.55262/fabadeczacilik.1766297

View : 176 | Download : 289

Publication Date : 2025-10-30

Article Type : Research Paper

Abstract :Fixed-dose combination (FDC) of antihypertensive drugs improve efficacy, safety, and patient adherence over monotherapy. However, a FDC of telmisartan (TEL) and indapamide (IND), both poorly soluble BCS Class II drugs, has not been available yet. This study aimed to develop an orodispersible film (ODF) containing TEL and IND cyclodextrin (CD) inclusion complexes (ICs) to enhance solubility and offer a patient adherence dosage form. In the first phase of the study, phase-solubility analysis was performed with β-CD then the ICs were prepared via kneading and assessed for solubility enhancement and entrapment efficiency. In the second phase, ICs were incorporated into hydroxypropyl-methylcellulose (HPMC) based ODFs using solvent casting. The films were characterized for thickness, mass and content uniformity, surface pH, water content, folding endurance, Young’s modulus, FTIR, in vitro disintegration and dissolution. AL-type phase-solubility plots confirmed 1:1 complexation and enhanced solubility by 1.7–4.1 fold, with entrapment efficiency >95%. ICs-loaded ODFs were thin (0.138 mm), uniform in mass (236.39 mg) and content (TEL 97.22%, IND 102.09%), nearly neutral pH, and low in water (2.68%). Mechanical testing showed adequate flexibility and stiffness (100 N.mm⁻² modulus). Disintegration occurred in <35 s. Dissolution exceeded 90% for both drugs within 15 min in 6.8 phosphate buffer, wheras in 0.1N HCl, TEL showed complete release in 15 min and IND reached 97% after 20 min. In conclusion, TEL and IND ICs–loaded HPMC ODFs successfully overcame solubility limitations, offering an immediate-release formulation across the gastrointestinal pH range with favorable physicochemical properties and potential to improve patient adherence.
Keywords : çözünürlük artırma, sabit doz kombinasyonları, ağızda dağılan film, siklodekstrin, telmisartan, indapamid

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