Role of Additives like Polymers and Surfactants in the Crystallization of Mebendazole

Abstract

Crystallization in the presence of additives like surfactants and polymers is a relatively less explored area but is important for polymorphic screening of a compound during its developmental stage. Surfactants and polymers act by various mechanisms to in‰uence either the growth or the nucleation phase, resulting in modiˆcation of either the polymorphic form or the crystal habit. The present study was aimed at understanding the crystallization behavior of the model drug mebendazole (MBZ) in the presence of an inert polymer polyvinyl pyrrolidone (PVP) and an anionic surfactant sodium lauryl sulphate (SLS). Crystals were generated by the antisolvent approach using the surfactant and polymer solutions in water as the antisolvents. Change in habit from needles to plates took place as a result of modiˆca-tion of the crystallization process in the presence of additive molecules. This was conˆrmed by quantiˆcation of these additives using speciˆc analytical methods, which revealed their presence in small amounts in theˆnal product (0.02, 0.15, and 0.24％ w/w SLS in crystals generated using 0.5, 1.0, and 2.0％ SLS, respectively, and 0.94, and 1.24％ w/w PVP K30 and PVP K90, respectively). Their presence in the crystals led to modiˆcation in the dissolution of the drug. SLS improved the extent of dissolution while PVP had a negative impact and led to reduction in the amount of MBZ released even below that of the pure drug. The study highlights the in‰uence of polymeric and surfactant additives on the crystallization process leading to modiˆed performance.

Dissolution enhancement of chlorzoxazone using cogrinding technique

“…The X-ray powder diffraction patterns of chlorzoxazone and optimized samples were recorded using PANalytical diffractometer system (XpertproPW30-40/60) with a copper target and scintillation counter detector (voltage 40 kV; current 30 mA; scanning speed 0.05°/s). [ 39 40 41 ] The sample holder was non-rotating and temperature of acquisition was room temperature. The diffraction pattern was analyzed in a specific 2θ range.…”

Formulation and In- Vitro Evaluation of Spherical Crystal Agglomerates of Ebastine by Quasi Emulsion Solvent Diffusion Method

“…This increase was mainly related to spherical shape of SCAs and by increasing in wettability due to the presence of different polymers. PEG 4000 show highest increase in rate of dissolution (f2=20.014) in comparison with pure drug dissolution rate that's because PEG 4000 have important effect on maintaining the spherical shape of agglomerated crystal (36) and also it enhances the physical and chemical stability of drugs and prevents aggregation of the drug particles as a result of the steric hindrance and/or masking of charges provided through formation of a conformational cloud (37) so, higher surface area will be available for dissolution. β.cyclodextrin and TPGS increase in dissolution of EBS (f2= 24.07294) and (f2= 39.46175) respectively due to improvement in solubility.…”

Understanding Pharmaceutical Polymorphic Transformations II: Crystallization Variables and Influence on Dosage Forms

“…Reduction in particle size was also observed in case of mebendazole when crystallized in presence of SLS. Further SLS also influenced the crystal habit by favoring plate type structure instead of needles [82]. On the other hand, if a surfactant has affinity towards a specific face of crystal by virtue of hydrogen bonding, it is more likely to restrict molecular mobility of the API and interfere with structural changes [83,84].…”