INFLUENCE OF FOOD INDUCED VISCOSITY ON DISSOLUTION AND DISINTEGRATION OF TABLETS: EFFECT OF FORMULATION AND PROCESS PARAMETERS ON TABLET MANUFACTURED BY WET GRANULATION
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Date
2023-06-05
Authors
Zain Alabedin Zanoon
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Abstract
Abstract
Postprandial elevation in gastric viscosity may retard tablet disintegration and delay drug dissolution from solid dosage forms, resulting in a significant decrease in drug bioavailability thereby affecting the therapeutic efficacy. This may be critical especially for medication where rapid onset of action is required. Deep understanding of the critical processing parameters on tablet disintegration and drug dissolution under fed conditions will help in designing a formulation with minimum viscosity mediated negative food effects.
The current research aims to study the impact of formulation and processing factors on tablet disintegration and release of Active Pharmaceutical ingredient (API) under both fasting state and fed states. The effect of different types of fillers was investigated in different formulations: Lactose monohydrate, corn starch and Microcrystalline cellulose (MCC), as well as, Di-calcium phosphate dehydrate. Wet granulation is a critical manufacturing step for oral solid dosage forms. Wet granulation method was applied in the preparation of ten immediate release formulations with Paracetamol serving as the model drug. The effects of wet granulation parameters such as: the mode of incorporation of disintegrant and the type of the granulating solvent were highlighted.
The study concluded that filler type is found to affect tablet disintegration: MCC based formulations gave the quickest drug disintegration in simulated fasted state, but they were the worst under viscous media. Lactose and Dicalcium Phosphate (DCP) based formulations provide rapid disintegration under fed state. Formulations prepared by using alcohol as solvent of granulation had shorter disintegration times compared to formulations using water in both fasting and fed states. The addition of Sodium Starch Glyclolate (SSG) intra-granularly results in shorter disintegration time compared to the extra-granular counterparts under fed condition.
The study recommends that: the obtained results highlight the importance of formulation excipients (filler type) and manufacturing parameters on tablet disintegration. This study will provide guidance that help in design and development of formulation with minimal food effect.
Keywords: Behaviour; Disintegration; Dissolution; Even Formula; Fasting State; Fed State; Odd Formula.