ABSTRACT
Four different approaches were followed for the development of a HPLC method for the determination of meglumine in solid dosage formulations: derivatization of meglumine prior to HPLC analysis, the use of an ion-pairing reagent in the mobile phase, the use of charged surface hybrid stationary phase and the use of a column designed for carbohydrate separations. The method using anionic pairing reagent in the mobile phase was shown to be suitable for the quantitative determination of meglumine in solid dosage forms. The HPLC separation was achieved on an Agilent Eclipse XDB-C18 column (150 mm x 4.6 mm, 3.5 microm particle size) using a mobile phase with octane-1-sulfonic acid. The method was validated and validation included the following studies: selectivity, precision (repeatability), linearity and accuracy. During validation experiments RID and DAD detectors were used.
Subject(s)
Meglumine/analysis , Carbohydrates/analysis , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Chromatography, Ion Exchange , Excipients/analysis , Indicators and Reagents , Pharmaceutical Preparations/analysis , Refractometry , Reproducibility of Results , Surface PropertiesABSTRACT
Synthesis of poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)]-thioglycolic acid (PHEA-TGA) conjugate as a new polyaspartamide thiomer is described. The parent polymer PHEA is chemically modified by introducing sulphydryl-bearing compound thioglycolic acid. By varying the reaction conditions several batches of PHEA-TGA conjugates were prepared and analyzed. Tensile studies revealed that total work of adhesion of PHEA-TGA increased more than twice compared to the unmodified polymer. Microparticles prepared from the thiolated polymer preserved its bioadhesive properties.
Subject(s)
Peptides/chemical synthesis , Polymers/chemical synthesis , Thioglycolates/chemical synthesis , Chemistry, Pharmaceutical/methods , Particle Size , Peptides/analysis , Polymers/analysis , Spectroscopy, Near-Infrared/methods , Technology, Pharmaceutical/methods , Thioglycolates/analysisABSTRACT
Inclusion complexation between piroxicam (PX) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) in the presence of hydroxypropyl methylcellulose (HPMC) was studied in aqueous solution and in the solid state. Phase solubility studies were used to evaluate the HPbetaCD complexation in the presence of HPMC. Stability constants, Ks, of the complexes were determined. The stability of the inclusion complex was improved in the presence of HPMC. Solid microspheres were obtained by spray drying, and were characterized by differential scanning calorimetry (DSC), regarding drug content, and particle size distribution. Scanning electron microscopy (SEM) was also used to characterize the systems prepared. In the solid system HPMC facilitated to some extent the drug dissolution due to increased solubility. The presence of HPMC and HPbetaCD in the microspheres promoted dissolution rate. Cyclodextrin complexation increased PX flux through a semipermeable membrane. Presence of HPMC in the system additionally increased the drug flux more than 80%, by increasing the drug solubility and consequently the affinity of the ternary complex for the aqueous diffusion layer in the donor compartment.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Piroxicam/chemistry , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin , Algorithms , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical , Excipients , Hypromellose Derivatives , Kinetics , Microscopy, Electron, Scanning , Microspheres , Particle Size , Permeability , Piroxicam/administration & dosage , SolubilityABSTRACT
Estradiol-3-benzoate (EB), an ester derivative of the main oestrogen hormone estradiol, was chemically modified and bound to poly(alpha,beta-(N-2-hydroxyethyl-DL-aspartamide))-poly(alpha,beta-(N-2-aminoethyl-DL-aspartamide)) copolymer (PAHA). EB was first converted to estradiol-3-benzoate-17-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EB. In PAHA-EB estradiol moiety was covalently bound to the polymeric carrier by carbamate linkage, through non-toxic ethylenediamine spacer. The synthesized compound is a potential hydrosoluble estradiol prodrug.
