Optimization of Sample Preparation and Analytical Performance Evaluation for a Model Polar Compound in Hydroxypropyl Methycelulose-Based Controlled-Release Tablets

Marijana Bozhinovska; Tina  Achkoska; Ana Atanasova; Packa  Antovska; Olga  Gigopulu; Ana  Poceva Panovska

doi:10.5937/arhfarm76-66354

Marijana Bozhinovska Research & Development, Alkaloid AD Skopje, Skopje, North Macedonia; Ss. Cyril and Methodius University, Faculty of Pharmacy, Skopje, North Macedonia
Tina Achkoska Research & Development, Alkaloid AD Skopje, Skopje, North Macedonia
Ana Atanasova Research & Development, Alkaloid AD Skopje, Skopje, North Macedonia
Packa Antovska Research & Development, Alkaloid AD Skopje, Skopje, North Macedonia
Olga Gigopulu Ss. Cyril and Methodius University, Faculty of Pharmacy, Skopje, North Macedonia
Ana Poceva Panovska Ss. Cyril and Methodius University, Faculty of Pharmacy, Skopje, North Macedonia

DOI: https://doi.org/10.5937/arhfarm76-66354

Keywords: hydroxypropyl methylcellulose, controlled-release tablets, polar compound, sample preparation, acetonitrile extraction, method performance evaluation

Abstract

Controlled-release (CR) tablets based on hydroxypropyl methylcellulose (HPMC) provide numerous therapeutic advantages, but pose significant analytical challenges during the assay of polar active substances due to the polymer’s high swelling capacity and gel-forming behaviour. This study aims to develop and evaluate a robust two-step sample preparation procedure that ensures complete extraction and accurate quantitation of a model polar basic compound incorporated into an HPMC matrix. Various diluents and agitation techniques were systematically compared to identify conditions enabling full recovery of the analyte. The optimized workflow involved initial extraction with acetonitrile for 15 minutes under ultrasonic agitation, followed by hydration with water for 45 minutes under magnetic stirring. The samples were analysed with High-performance liquid chromatography (HPLC) analysis, using ion-pair reversed-phase conditions. Acetonitrile effectively disrupted the HPMC network, preventing gel entrapment and yielding quantitative recovery (100 ± 0.5%) with excellent reproducibility (RSD < 1%). The analytical method demonstrated linearity (R² = 0.9997), accuracy (99.6 %), precision (RSD ≤ 0.5%), robustness, and solution stability consistent with ICH Q2 (R2) principles. The proposed two-step acetonitrile-water extraction provides a reliable, transferable strategy for the assay of polar drugs in HPMC-based controlled-release formulations and can serve as a methodological framework for future compound-specific validation.

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