Investigating the Effects of Formulation Variables on the Disintegration of Spray Dried Amorphous Solid Dispersion Tablets

Abstract

Amorphous solid dispersion (ASD) tablets based on hydrophilic polymer carriers may encounter disintegration challenges. In this work, the effect of different formulation composition variables on the ASD tablet disintegration performance was systematically studied. GDC-0334: copovidone (PVPVA) 60: 40 ASD prepared by spray drying was selected as the model ASD system. The effects of ASD loading, filler type and ratio, disintegrant type and level were then investigated using tablets made by direct compression process. Tablet disintegration time increased with the increase of ASD loading, especially when ASD loading exceeded 50%. At the same tablet solid fraction, when lactose was used as the soluble filler, faster tablet disintegration time was observed compared to the tablets with mannitol as the soluble filler. Among the three tested disintegrants, croscarmellose sodium performed the best in facilitating the ASD tablet disintegration, followed by sodium starch glycolate, and crospovidone was the poorest. When croscarmellose sodium was used as the disintegrant, 5% level was sufficient to enable ASD tablet disintegration at 60% ASD loading and further increase of croscarmellose sodium level to 8% did not provide additional benefit. Water uptake experiments were performed on selected tablets and the results demonstrated a positive correlation with tablet disintegration time, indicating water penetration is a major contributing step for the disintegration of our ASD tablets. Overall, this work provides a rationale for excipient selection and insights into building a platform formulation approach for developing immediate-release ASD tablets.

Introduction

In the past decades, an increasing percentage of small molecule drug candidates emerging from drug discovery pipeline are poorly water-soluble.¹ The need of solubility enhancement has hence become more imperative for the successful delivery of these compounds to achieve therapeutic exposure.² Amorphous solid dispersion (ASD) formulation has demonstrated to be an effective approach for enhancing the solubility of a drug without impacting its permeability.³ Since the initiation of developing ASD.

Materials

GDC-0334 active pharmaceutical ingredient (API) was synthesized by the Synthetic Molecule Process Chemistry department at Genentech Inc. The obtained API was an anhydrous crystalline free form with a purity greater than 99.5%. PVPVA (Kollidon VA64) was a generous gift from BASF (Florham Park, NJ). The following excipients were used in this study for ASD tablet formulation – microcrystalline cellulose or MCC (Avicel PH102, Dupont Inc., Wilmington, DE), lactose (Lactose Fast Flo® 316, Kerry Inc.).

Wei Zhang, Prajwal Thool, Benjamin W. Weitz, Hao Helen Hou, Investigating the Effects of Formulation Variables on the Disintegration of Spray Dried Amorphous Solid Dispersion Tablets, Journal of Pharmaceutical Sciences, 2024, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2024.09.024.