Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

Abstract

Abstract. Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.

Challenges to improve the biopharmaceutical properties of poorly water-soluble drugs and the application of the solid dispersion technology

“…The main obtaining methods for solid dispersions are briefly described below and their advantages and limitations are presented in Table 5. -Grinding can result in a mixture of amorphous and nanocrystalline drug, and the last can act as seeds to induce drug nucleation and recrystallization [13,14,34,35,36,47,48,49].…”

Application of Vibrational Spectroscopy to Study Solid-state Transformations of Pharmaceuticals

“…actually hinder drug release [209]. While for many systems a correlation between intermolecular interactions and crystal growth inhibition has been found as discussed below, other stabilization mechanisms are also debated and various examples have been reported where the IR spectrum did not differ significantly from that of the physical mixture [210,211,288] suggesting a lack of interaction at the molecular level. Resveratrol is a fast crystallizer and was selected by Wegiel et al for this reason as a model API to study the potential correlation between the strength of H bonding interactions between API and polymer in ASDs and crystallization inhibition [212].…”

Development, characterization and solubility enhancement of poorly water soluble drug telmisartan by polymer enriched bridging liquid technique using peg 4000 as hydrophilic polymer

“…The percentage drug content (Zhong et al, 2013) was determined by weighing about 10 mg of the crystal agglomerates, crushed and dissolved in 0.5ml of 0.1M NaOH and made up to 10ml with 7.5 Phosphate Buffer, vortexed for 15 min. It was iltered using 0.45µm syringe ilter (Merck Millipore) and analyzed UV spectrophotometrically at 296nm after suitable dilutions.…”