Spray-dried HPMC Microparticles of Indomethacin: impact of drug-polymer ratio and viscosity of the polymeric solution on dissolution

Polymeric microparticles prepared by spray-drying technique were investigated to enhance the dissolution rate of indomethacin [IM] in comparison with conventional microparticles prepared by co-precipitation solid dispersion method. Drug-polymer ratios and viscosity of polymeric solutions as potential factors were used in order to enhance the dissolution rate of IM. Spray-drying technique was used for preparing of microparticles using aqueous suspension of IM in hydroxypropyl methylcellulose [HPMC] polymer solution. The effect of drug-polymer ratios on dissolution rates of IM was studied in simulating intestinal medium. IM was analyzed spectrophotometrically at lambda=320 nm. For each drug-polymer ratios, low and high viscosity polymeric solutions were prepared and their impacts on the dissolution of IM were observed. Microparticles were morphologically characterized by optical microscopy. The interaction between IM and HPMC was studied by differential scanning calorimetry [DSC] and x-ray diffractometry [XRD]. Spherical fluffy microparticles of IM were obtained using HPMC. It was observed that the prepared spray-dried microparticles significantly increase the dissolution rate of IM. The increase in dissolution rates was achieved with drug: polymer ratios 1:1 as well as 1:2 and interestingly, the decrease in drug content in ratio exceeding 1:2 resulted in reduction in dissolution rates. Also, with all drug-polymer ratios, the low viscosity polymeric solutions gave the higher dissolution rates. In conclusion, HPMC microparticles loaded with IM were prepared by spray-drying technique and the potential of this technique to enhance the dissolution was studied. The findings indicate that the dissolution profile of IM microparticles prepared by spray-drying technique relied on drug-polymer ratios and viscosity of polymeric solutions

High performance liquid chromatographic method for determination of doxycycline in human plasma and its application in pharmacokinetic studies

An accurate, sensitive and reproducible high performance liquid chromatographic [HPLC] method for the quantitation of doxycycline in plasma has been developed and validated. The drug and the internal standard were eluted from a micro-Bondapak C [18] column [3.9 mm x 150 mm, I.D., 5 micro m particle size] at room temperature with a mobile phase consisting of acetonitrile and water [28:72,% v/v]. The flow rate was 0.8 ml/min. A UV detector set at 346 nm was used to monitor the effluent. Each analysis required no longer than 6 min. Quantitation was achieved by measurement of the peak area ratio of the drug to the internal standard. The limit of detection was 10.0 ng/ml and the limit of quantification of doxycycline in plasma was 0.10 micro g/ml. The standard curve ranged from 0.1 to 2.5 micro g/ml. The intraday coefficient of variation [C.V.,%] ranged from 1.444 to 3.016%, and interday [C.V.,%] from 1.572 to 2.705% at four different concentrations. The relative recoveries ranged from 98.43 to 105.13% and the absolute recoveries ranged from 54.08 to 62.56% at four different concentrations. Stability studies showed that doxycycline is stable for at least 4 weeks in plasma after freezing at - 20 °C. The method was applied for the determination of the pharmacokinetic parameters of doxycycline after oral administration of 100 mg capsules of two commercially available formulations to 6 human volunteers