Synchronic release of two hormonal contraceptives for about one month from the PLGA microspheres: in vitro and in vivo studies.
A controlled drug release system based on the injectable PLGA microspheres loaded with gestodene and ethinyl estradiol was prepared and evaluated for the feasibility of monthly synchronic delivery of the two hormonal contraceptives. The scanning electron microscopy, light-scattering analyzer and gel permeation chromatography were used to study the morphology, particle size and molecular weight of the polymer microspheres, respectively. HPLC was utilized to determine the drug loading and the drug released, while a LC-MS-MS system was employed to analyze the plasma drug concentration. Result indicated that the PLGA particles obtained were spherical and appropriate in size. The formulation was stable during the test period. In vitro drug release from the microspheres for both drugs was sustained for about 30 days mostly by the diffusion mechanism. The plasma drug concentration-time profiles of the drug-loaded microspheres were relatively smooth after subcutaneous injection to rats for about 1-month, compared with that for drug suspension. In vitro and in vivo correlation was established. One of the most important facts is the synchronicity of the two contraceptives both in the release kinetics in vitro and the pharmacokinetic behaviors in vivo. Therefore, the synchronic delivery of two contraceptives is achieved for about 1 month by using the injectable PLGA-based microspheres.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Yi
Y
Sun
Jiancheng
J
Wang
Xuan
X
Zhang
Zhijun
Z
Zhang
Yan
Y
Zheng
Dawei
D
Chen
Qiang
Q
Zhang
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D004967:Estrogens / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008863:Microspheres; D008970:Molecular Weight; D009652:Norpregnenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011136:Polysorbates / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014783:Viscosity
D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004967:Estrogens; D009652:Norpregnenes; D011136:Polysorbates; C033273:Gestodene; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004997:Ethinyl Estradiol; D002266:Carboxymethylcellulose Sodium