Enhancing flowability of lamivudine through quasi-emulsion solvent-diffusion (QESD) crystallization: A comprehensive study on surfactant impact, particle morphology by QbD concepts and tablet compression challenges

• Published in: European journal of pharmaceutical sciences Vol. 200; p. 106835
• Main Authors: Sreeharsha, Nagaraja, Gajula, Lakshmi Radhika, S, Srikruthi K, Bhavani, Penmetsa Durga, Goudanavar, Prakash, A, Rakshitha, Naveen, N Raghavendra, Shiroorkar, Predeepkumar Narayanappa, Meravanige, Girish, Telsang, Mallikarjun, Asif, Afzal Haq, Sreenivasalu, Pavan Kumar Pavagada
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024
• Subjects: Direct compression; Lamivudine; Optimization; Quality by design; Quasi-emulsion solvent diffusion; Lamivudine; Quasi-emulsion solvent diffusion; Direct compression; Quality by design; Optimization; Direct Compression; Quality By Design
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2024.106835

Lamivudine (LMD), an enantiomer of 2′-deoxy-3′-thiacytidine, plays a crucial role in combatting HIV-1 and managing hepatitis B virus infections. Despite its effectiveness, challenges arise from its difficult flowability and tendency to agglomerate during storage, necessitating a granulation step before tablet compression, as direct compression has proven ineffective. This study aimed to optimize Lamivudine spherical agglomerates using response surface methodology, delving into the intricate relationship between design factors (concentration of tween, span, and acetone) and experimental outcomes (yield and particle size) through central composite design. Analysis of variance (ANOVA) was employed for optimization, with the Quasi-emulsion solvent-diffusion (QESD) crystallization technique utilized for the checkpoint batch. This technique, involving a single solvent and antisolvent with surfactants, showcased remarkable enhancements in flowability and reduced storage agglomeration. The impact of various surfactants [Hydroxy Propyl Methyl Cellulose (HPMC), polysorbate 80, and sorbitane monooleate] on particle morphology, flowability, and storage agglomeration during crystallization was thoroughly assessed. While achieving direct compression into tablets, the porous structure of LMD agglomerates presented challenges in tablet press production speeds, prompting adjustments such as reducing punch speed or implementing a precompression step. Positive outcomes were realized for disintegration and in vitro drug release in comparison to direct compression and wet granulation methods. In conclusion, the QESD crystallization technique successfully yielded hollow, spherical LMD agglomerates with enhanced properties, representing a significant milestone in pharmaceutical formulation. [Display omitted]