title: Solvent, emulsifier and drug concentration factors in poly(D,L-lactic acid) microspheres containing hexamethylmelamine.
abstract: Biodegradable poly(D,L-lactic acid) (PLA) microspheres containing hexamethylmelamine (HMM) were developed for potential use in chemoembolization and intraperitoneal implantation. The emulsion-solvent-evaporation/extraction method was used to prepare 15 formulations with different drug/polymer ratios, solvent compositions and emulsifer concentrations in the continuous aqueous phase. A central composite experimental design was used, with five levels of the three different factors. All formulations resulted in the formation of discrete matrix microspheres containing crystalline drug. The mean particle sizes of the microsphere formulations ranged from 62-348 microm and the effect of the independent variables on microsphere size was satisfactorily predicted using response surface methodology. For theoretical drug loads of 5-40%, efficiency of entrapment ranged from 75-107% and porosities of the microspheres were between 0-6.5%. The rate of drug release from the microspheres depended on drug loading and particle size. Microspheres with 22.5% or greater theoretical drug content released drug rapidly, with almost complete release occurring in 70 h or less. Formulations with drug loading of 5% and 9.57%, however, released drug very slowly, with less than 50% released in 40 days. Release kinetics of narrow sieve cuts of microspheres with high drug load (35.4%) followed square root of time profiles.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hariharan
authors.forename: J C
authors.initials: JC
authors.lastname: Price
mesh_terms: D006585:Altretamine / Q000008:administration & dosage* / Q000737:chemistry*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003720:Densitometry; D004655:Emulsions; D005079:Excipients; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D012997:Solvents
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004655:Emulsions; D005079:Excipients; D011091:Polyesters; D011108:Polymers; D012997:Solvents; D019344:Lactic Acid; C033616:poly(lactide); D006585:Altretamine