polymorph

Carbamazepine; an antiepileptic drug, exists in various polymorphic forms out of which Form III is extensively studied as a model  form for  cocrystallization. The main focus of the present study was to cocrystallize Carbamazepine form III with Itaconic acid as a coformer by solvent evaporation technique using Acetone (Class III) as the solvent medium for drug and coformer interaction at molecular level. The obtained Carbamazepine cocrystals were evaluated for parameters like Visual morphology, differential scanning calorimetry, infrared spectroscopy, x-ray diffractometry, contact angle, drug content uniformity, flow properties and in vitro drug release testing. A comparison of the cocrystal characteristics was made with a physical mixture of Carbamazepine with itaconic acid inorder to confirm an interaction at a molecular level between the drug and coformer. The obtained carbamazepine cocrystals showed distinct difference in its morphological characteristics as compared to plain drug. Additionally, the cocrystals showed presence of additional peaks in differential scanning calorimetry thermograph as well as bandshifts in the infrared spectrum. The X-Ray diffractogram of cocrystals was found to show a shift towards left thus confirming a change in the crystal lattice. In vitro drug release testing of cocrystals showed an increase in drug release when compared to drug release from physical mixture and plain drug when tested in 1% Sodium lauryl sulphate. Hence Solvent evaporation technique was found to be successful in producing cocrystals of Carbamazepine polymorph III with Itaconic acid as a coformer.

This study evaluated the dissolution behaviour of a novel amorphous form (Form A) and the commercially preferred crystalline form (Form I) of efavirenz. Generally, amorphous forms tend to achieve a greater extent and rate of dissolution compared to their crystalline counterparts. The results showed that the dissolution of Form A to be significantly lower than that of Form I due to agglomeration. Factors which contributed to the agglomeration behaviour of Form A include: high surface free energy, a lower degree of wetting, and the low glass transition temperature of Form A which caused the sample to convert to the rubber phase which is stickier. The agglomeration increased the relative particle size thereby reducing the exposed surface area of Form A; ultimately reducing the rate and extent of dissolution. The dissolution behaviour of Form A was found to be dependent on sample size and surfactant (SLS) concentration. Scanning Electron Microscopy (SEM) was employed to investigate surface area properties which provided information supporting the powder dissolution results. The solubility and intrinsic behaviour of the two forms were found to be comparable. Upon further investigation it was found that Form A undergoes phase mediated transformation into Form I during the solubility and dissolution experiments and that this too contributed to the apparent dissolution and solubility behaviour of Form A.  It was found the nucleation rate of Form A was potentiated by higher SLS content in the dissolution medium. Keywords: polymorph, amorph, dissolution, solubility, efavirenz.