Evaluation of the quality of the fixed-dose triple combination dispersible tablet for HIV-positive paediatric population after the continuous direct compression and batch manufacturing techniques

Abstract

Introduction

Currently, the paediatric population with positively tested human immunodeficiency virus (HIV) is facing challenges in the administration of off-label and manipulated pharmaceutical products due to the lack of dosage forms specifically designed and authorised for paediatric use. This issue raises concerns regarding medication safety, unavailability of appropriate medications, and improper use of existing treatments. Although paediatric patients prefer liquid and powder formulations, the stability of liquid dosage forms and compatibility of powders with many dietary products remain unresolved.

Aim

The aim of this study was to investigate the robustness in the quality and dissolution profiles of fixed-dose dispersible tablets with three different active pharmaceutical ingredients (API) (abacavir sulphate, tenofovir disoproxil fumarate and zidovudine) after utilising continuous direct compression (CDC) and batch manufacturing methods with implemented Design-of-Experiments (DoE).

Methods

The powder and tablet properties were evaluated employing quality standards of the European Pharmacopoeia (Ph. Eur.). CDC and batch process methods were used to produce fixed-dose combinations (FDC) of dispersible tablets with the aid of DoE which involved varying mixing speeds and breaking forces.

Results

The results indicated that CDC and batch methods could offer similar tablet quality attributes in terms of the physical properties of the tablets and dissolution profiles. The dissolution profiles of 15 min indicated that all six DoE points and the batch of tenofovir disoproxil fumarate met the European Pharmacopoeia standard of greater than 80 % of the drug release for immediate-release dosage forms. For abacavir sulphate the tablets from five out of six DoE points and the batch met the acceptable dissolution criteria. For zidovudine, only two DoE points met the acceptable criteria for the dissolution profile which might be related to the physical properties of the API. Moreover, pre-blending could be used to enhance the flowability of APIs and excipients with poor flowability.

Conclusion

FDC dispersible tablets were successfully manufactured with CDC and batch methods. Moreover, the product integrity results were similar for both the production technologies. However, the formulation and pre-blends require further optimization particularly for poorly flowable active pharmaceutical ingredients.