In vitro and in vivo release of poly(DL-lactic acid) microspheres containing neurotensin analogue prepared by novel oil-in-water solvent evaporation method
| Autor: | Ryoichi Machida, Sumio Watanabe, Ichiro Yamakawa, Yuki Tsushima |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Stereochemistry Polymers Injections Subcutaneous Polyesters Kinetics Molecular Sequence Data Pharmaceutical Science Dosage form chemistry.chemical_compound Subcutaneous injection stomatognathic system Pharmacokinetics In vivo Animals Amino Acid Sequence Lactic Acid Rats Wistar Active ingredient Neuropeptides Hydrogen-Ion Concentration Microspheres Rats chemistry Delayed-Action Preparations Lactates Liberation Oligopeptides Nuclear chemistry Neurotensin |
| Zdroj: | Journal of pharmaceutical sciences. 81(8) |
| ISSN: | 0022-3549 |
| Popis: | Poly(DL-lactic acid) (PLA) microspheres containing a neurotensin analogue [NA; H(CH3)—Arg—Lys—Pro—Trp—tert-Leu-Leu—OEt · 3HCl] were prepared by a novel oil-in-water (o/w) solvent evaporation method, and the release behaviors were evaluated in vitro. About 20% of the loaded NA was released initially, and the subsequent release lasted for a month from microspheres prepared with PLA of molecular weight 2000 (PLA 2000). A smaller initial release from PLA 4000 and PLA 6000 microspheres was found, but a lag time of 2–3 weeks during which the drug was not released was observed with PLA 4000 and PLA 6000 microspheres. The addition of relatively hydrophilic monoglycerides decreased the lag time, and a fairly constant release of NA was achieved. The pharmacokinetic behavior of NA from PLA 2000 microspheres was studied in rats. The release of the drug after a subcutaneous injection exhibited pseudo-zero-order kinetics for 1 month. The initial release of the drug from the microspheres was reflected in a sharp increase of the plasma levels of the de-ester form of NA [H(CH3)—Arg—Lys—Pro—Trp—tert-Leu—Leu—OH], and the subsequent steady-state levels agreed well with the predicted levels obtained from analysis of constant-infusion kinetics. |
| Databáze: | OpenAIRE |
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