Aceclofenac (AC) is a phenyl acetic acid derivative [2-(2',6'-dichlorophenyl)amino] phenylacetoxyacetic acid], a novel NSAID indicated for the symptomatic treatment of pain and inflammation (1). The short biological half-life (about 4 h) and high frequency of dosing make aceclofenac an ideal candidate for sustained release. The bioadhesive microspheres of aceclofenac would prolong the residence time at the absorption site to facilitate intimate contact with the absorption surface and thereby improve and enhance bioavailability and increase patient compliance. Natural hydrophilic polymers like alginate and pectin are widely used in numerous biomedical applications for their bioadhesion properties. Alginic acid and pectin are natural polysaccharides that are widely Ionotropic gelation was used to entrap aceclofenac into algino-pectinate bioadhesive microspheres as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Microspheres were investigated in vitro for possible sustained drug release and their use in vivo as a gastroprotective system for aceclofenac. Polymer concentration and polymer/drug ratio were analyzed for their influence on microsphere properties. The microspheres exhibited good bioadhesive property and showed high drug entrapment efficiency. Drug release profiles exhibited faster release of aceclofenac from alginate microspheres whereas algino-pectinate microspheres showed prolonged release. Dunnet's multiple comparison analysis suggested a significant difference in percent inhibition of paw edema when the optimized formulation was compared to pure drug. It was concluded that the algino-pectinate bioadhesive formulations exhibit promising properties of a sustained release form for aceclofenac and that they provide distinct tissue protection in the stomach.
Effects of drug solubility on the release kinetics of water soluble and insoluble drugs from HPMC based matrix formulations The purpose of the present research work was to observe the effects of drug solubility on their release kinetics of water soluble verpamil hydrochloride and insoluble aceclofenac from hydrophilic polymer based matrix formulations. Matrix formulations were prepared by the direct compression method. The formulations were evaluated for various physical parameters. Along with the dynamics of water uptake and erosion, SEM and in vitro drug release of the tablets were studied. Applying an exponential equation, it was found that the kinetics of soluble drug release followed anomalous non-Fickian diffusion transport whereas insoluble drug showed zero-order release. SEM study showed pore formation on the tablet surface that differed depending on drug solubility. t-Test pointed to a significant difference in amount of both drugs released due to the difference in solubility. Solubility of the drug effects kinetics and the mechanism of drug release.
In this present research, an attempt has been made to address the influence of drug-coformer stoichiometric ratio on cocrystal design and its impact on improvement of solubility and dissolution, as well as bioavailability of poorly soluble telmisartan. The chemistry behind cocrystallization and the optimization of drug-coformer molar ratio were explored by the molecular docking approach, and theoretical were implemented practically to solve the solubility as well as bioavailability related issues of telmisartan. A new multicomponent solid form, i.e., cocrystal, was fabricated using different molar ratios of telmisartan and maleic acid, and characterized by SEM, DSC and XRD studies. The molecular docking study suggested that specific molar ratios of drug-coformer can successfully cluster with each other and form a specific geometry with favourable energy conformation to form cocrystals. Synthesized telmisartan-maleic acid cocrystals showed remarkable improvement in solubility and dissolution of telmisartan by 9.08-fold and 3.11-fold, respectively. A SEM study revealed the formation of cocrystals of telmisartan when treated with maleic acid. DSC and XRD studies also confirmed the conversion of crystalline telmisartan into its cocrystal state upon treating with maleic acid. Preclinical investigation revealed significant improvement in the efficacy of optimized cocrystals in terms of plasma drug concentration, indicating enhanced bioavailability through improved solubility as well as dissolution of telmisartan cocrystals. The present research concluded that molecular docking is an important path in selecting an appropriate stoichiometric ratio of telmisartan: maleic acid to form cocrystals and improve the solubility, dissolution, and bioavailability of poorly soluble telmisartan.
Purpose: The sole purpose of this study is to improve the solubility and dissolution of telmisartan by cocrystallization technique and apply computational simulation approach to assess the nature of chemical interactions between telmisartan and coformer as well as the solvent contribution to the molecules for furnishing cocrystallization. The effects of various concentration of coformer i.e. oxalic acid on physicochemical parameters and drug release were investigated. Results: Solubility studies suggested that cocrystallization technique with oxalic acid helps to increase the solubility of pure telmisartan of about 7 folds and drug release study revealed that telmisartan-oxalic acid cocrystals showed greater dissolution as compared to pure telmisartan. SEM study suggested that prepared telmisartan cocrystals showed rhomboid-shaped crystals with sharp edges and smooth surface. FTIR study revealed that shifting in the vibrational frequencies of C=O group of telmisartan in telmisartan-oxalic acid cocrystal indicates the formation of supra molecular hetero synthon of the cocrystal. DSC and XRD study confirmed the formation of telmisartan-oxalic acid cocrystals. Computational simulation approach revealed that, telmisartan and oxalic acid can interact each other in presence of methanol and water where oxalic acid can form interactions principally with the others. The interactions, thereof, may form several associations or bondings in between the drug and carrier modifying the planarity, bond energy, bond angles of the both which subsequently lead to cocrystallization. Conclusion: So, the present research concluded that prepared telmisartan-oxalic acid cocrystal is a successful application of crystal engineering approach to improve the physicochemical properties as well as to enhance the solubility and dissolution of telmisartan.
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