Influence of excipients and processing conditions on the development of agglomerates of racecadotril by crystallo-co-agglomeration

Abstract

Purpose:The purpose of the present investigation was to improve the flow and mechanical properties of racecadotril by a crystallo-co-agglomeration (CCA) technique. Direct tableting is a requirement of pharmaceutical industries. Poor mechanical properties of crystalline drug particles require wet granulation which is uneconomical, laborious, and tedious.Materials and Methods:The objective of this work was to study the influence of various polymers/excipients and processing conditions on the formation of directly compressible agglomerates of the water-insoluble drug, racecadotril, an antidiarrheal agent. The agglomerates of racecadotril were prepared using dichloromethane (DCM)–water as the crystallization system. DCM acted as a good solvent for racecadotril as well as a bridging liquid for the agglomeration of the crystallized drug and water as the nonsolvent. The prepared agglomerates were tested for micromeritic and mechanical properties.Results:The process yielded ~90 to 96% wt/ wt spherical agglomerates containing racecadotril with the diameter between 299 and 521 μ. A higher rotational speed of crystallization system reduces the size of the agglomerates and disturbs the sphericity. Spherical agglomerates were generated with a uniform dispersion of the crystallized drug. CCA showed excellent flowability and crushing strength.Conclusion:Excipients and processing conditions can play a key role in preparing spherical agglomerates of racecadotril by CCA, an excellent alternative to the wet granulation process to prepare intermediates for direct compression.

Design and evaluation of sustained release spherical agglomerates of Fluvastatin sodium by crystallo-co-agglomeration

“…Sometimes, good solvent also serves as bridging liquid. Presence of suitable excipient greatly affects the properties of agglomerates (Garala et al, 2012;Raval et al, 2013). Utilization of CCA in designing spherical agglomerates having excellent micromeritic and compression properties with satisfactory mechanical strength has been revealed in various studies.…”

Spherical Crystallization of Drugs

“…Due to the hydrophobic nature of most excipients, incorporation of them in the formed agglomerates using organic bridging liquid is complicated [71,72]. Then spherical agglomeration could not be employed for low-dose or poorly compressible materials.…”

Design and Development of Crystallo-co-agglomerates of Ritonavir for the Improvement of Physicochemical properties.

“…In particular, improvement in the efficiency of the manufacturing process and a high degree of particle functionality can be achieved by these techniques. 5 Crystallo-co-agglomeration (CCA) is a novel particle engineering technique, which aggregates crystals of drugs in the form of small spherical particles using excipients and solvents to develop an intermediate material with improved micromeritic and mechanical properties, solubility, and dissolution. The rate of dissolution of the drug from the agglomerates or compacts thereof can be improved and modified by using suitable excipients during the process of preparation of agglomeration.…”