The effect of egg albumin on the crystalline properties of carbamazepine in sustained release hydrophilic matrix tablets and in aqueous solutions

• Published in: Journal of controlled release 2000-04, Vol.65 (3), p.331-343
• Main Authors: Katzhendler, Ifat, Azoury, Reuven, Friedman, Michael
• Format: Article
• Language: English
• Subjects: Anticonvulsants - administration & dosage; Anticonvulsants - chemistry; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Calorimetry, Differential Scanning; Carbamazepine; Carbamazepine - administration & dosage; Carbamazepine - chemistry; Carbamazepine dihydrate; Crystallinity; Crystallization; Delayed-Action Preparations; Differential scanning calorimetry; Egg albumin; General pharmacology; Kinetics; Medical sciences; Microscopy, Electron, Scanning; Neuropharmacology; Ovalbumin - chemistry; Pharmaceutical Solutions; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Polymorphism; Scanning electron microscopy; Solubility; Surface Tension; Sustained release; Tablets; X-Ray Diffraction
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(99)00124-8

The influence of egg albumin (EA) on the crystal habit properties of carbamazepine (CBZ) in aqueous solutions, solid-state, and in sustained release matrix tablets was investigated using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and contact angle goniometer (CAG). The results suggest that in solid-state mixtures, EA affected the polymorphic transitions of CBZ from the β to the α form. In hydrated matrix tablets and aqueous solutions, EA influenced the conversion rate of CBZ to the dihydrate form depending on EA concentration. It was found that increasing EA concentration enhanced CBZ dihydrate aggregation, an effect that leads to the formation of crystals with high mechanical strength and decrease of CBZ solubility. Possible mechanisms, which explain crystal growth and aggregation, as well as alteration of CBZ polymorphic transitions in the solid-state, gel layer, and in aqueous solution were suggested. In the gel layer of hydrated tablets the kinetics of CBZ transformation to the dihydrate form, crystal growth and aggregation were influenced by various processes: matrix hydration, erosion mechanism and the formation of metastable conditions, which favor aggregation and growth. The release kinetics of CBZ from the matrix highly correlated with the crystalline and morphological changes occurring in the matrix.