Improved physicochemical characteristics of artemisinin-nicotinamide solid dispersions by solvent evaporation and freeze dried methods

Artemisinin [ARMN] is a drug of choice against drug-resistant malaria especially due to Plasmodium falciparum. Being poorly soluble in water, its solid dispersions with nicotinamide [NA] were prepared at various drug-carrier ratios [1:1, 1:4, 1:6, 1:8, 1:10] by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery [DSC], fourier transform infrared spectroscopy [FTIR], X-ray diffraction patterns [XRD], phase solubility and dissolution studies. Artemisinin and nicotinamide both were found completely crystalline as shown by their XRD patterns. Physical mixtures [PMs] showed decreased intensity in their XRD patterns while solid dispersions by solvent evaporation method [SLVPs] exhibited displaced angles and decreased intensity whereas freeze dried solid dispersions [FDSDs] showed least number of peaks having low intensity and maximum displaced angles. DSC thermograms of drug-carrier ratios at 1:1-1:4 showed lower melting temperature than artemisinin and nicotinamide in all preparations. Endothermic temperature of artemisinin in PMs and SLVPs increased with rise of nicotinamide content upto 1:6 ratio followed by decline. All samples showed crystallization temperature below the artemisinin except drug-carrier ratio 1:6 of PMs while delta H value was minimum at this ratio. FDSDs produced lowest endothermic temperature than corresponding PMs and SLVPs. SLVPs exhibited band shifting in both functional and fingerprint region compared to respective PMs as exhibited by their FTIR spectra. FDSDs and SLVPs showed different nature of bonding among artemisinin and nicotinamide. FDSDs produced strongest CONH[2] bonding followed by SLVPs and PMs respectively. PMs produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. SLVPs exhibited improved solubility and dissolution profile corresponding to PMs. FDSDs showed highest release rate and aqueous solubility followed by SLVPs and PMs at all ratios. PMs and SLVPs showed their highest dissolution profile at 1:6 drug-carrier ratio followed by gradual decrease while FDSDs progressed in dissolution rate with increase of nicotinamide content successively upto maximum at 1:10 ratio

Preparation, characterization and release of verapamil hydrochloride from polycaprolactone/ acrylic acid [PCL/AA] hydrogels

In this study pH sensitive, biocompatible and controlled released hydrgels were prepared and their localized drug delivery effect was analyzed. Polycaprolactone and acrylic acid [PCL/AA] were reacted by free radical polymerization and developed inter penetrating polymeric network [IPN] hydrogels. Benzylperoxide was used as initiator and N, N methylenebisacrylamide [NNMBisAm] was employed as a cross-linking agent. Different concentrations of monomer, polymer and cross-linking agent were used and the reaction parameters were optimized. The obtained PCL/AA hydrogels were fully characterized by Fourier transform infrared spectroscopy [FT-IR], scanning electron microscopy [SEM], and thermogravimetric analysis [TGA] that determined the polymer structure, its morphology and strength respectively. Verapamil, a calcium channel blocker was loaded by incubation of polymerization method. Controlled release Verapamil hydrogel was developed due to its low solubility; low permeability and having very short half life of 1.2-2 h. The dynamic swelling, equilibrium swelling and drug release were carried out in a buffer solution of pH 1.2, 4.5 and 6.8. Concentration of Acrylic acid showed direct, while Polycaprolactone inverse relation to swelling and drug release due to their hydrophilic and hydrophobic nature respectively. Cross-linking agent also had the contrary effect on swelling. Diffusion coefficient [D] of hydrogels was determined by using Flory-Rehner theory. Drug release and swelling data were analyzed by different kinetic models, like Zero order, First order, Higuchi, Korsmeyer's and Peppas. The release and diffusion was best described by the first order kinetics where n value was <0.5 for all the formulations indicating Fickian drug release mechanism

Study of the characteristics and some pharmaceutical aspects of homo and copolymers of vinyl alcohol

Degree of hydrolysis has a key role in the properties of polyvinyl alcohol and its copolymers. Degree of hydrolysis affects swelling, thermal behaviour as well as release of incorporated drugs. However, these properties are also affected by the composition of the copolymers and degree of crosslinking. Furthermore degree of swelling and drug release decreased by increasing the crystallinity in the copolymer