A novelin vitro release technique for peptide-containing biodegradable microspheres

Kostanski, Janusz W.; DeLuca, Patrick P.

doi:10.1007/bf02830519

Cited by 18 publications

(21 citation statements)

References 29 publications

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“…11 In the present study, however, the purpose was to investigate the formation of acylated peptide, hence a PBS media was also utilized to study the effect of physiological pH on the extent of reaction. In PBS buffer media alone, octreotide acetate does not display any significant instability for 21 days at 37(C with an apparent first order degradation constant of 4.37 × 10 -3 days -1 (unpublished laboratory data from University of Kentucky).…”

Section: In Vitro Release In Acetate and Phosphate Buffer Systemsmentioning

confidence: 99%

Identification of chemically modified peptide from poly(D,L-lactide-co-glycolide) microspheres under in vitro release conditions

et al. 2003

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ABSTRACTmers within polymeric microspheres. The data suggest that due to steric hindrance factors, polymers with greater lactide content were less amenable to the formation of adduct impurities compared with PLGA 50:50 copolymers.The purpose of this research was to study the chemical reactivity of a somatostatin analogue, octreotide acetate, formulated in microspheres with polymers of varying molecular weight and co-monomer ratio under in vitro testing conditions. Poly(D,L-lactide-coglycolide) (PLGA) and poly(D,L-lactide) (PLA) microspheres were prepared by a solvent extraction/evaporation method. The microspheres were characterized for drug load, impurity content, and particle size. Further, the microspheres were subjected to in vitro release testing in acetate buffer (pH 4.0) and phosphate buffered saline (PBS) (pH 7.2). In acetate buffer, 3 microsphere batches composed of low molecular weight PLGA 50:50, PLGA 85:15, and PLA polymers (≤10 kDa) showed 100% release with minimal impurity formation (<10%). The high molecular weight PLGA 50:50 microspheres (28 kDa) displayed only 70% cumulative release in acetate buffer with significant impurity formation (~24%). In PBS (pH 7.4), on the other hand, only 50% release was observed with the same low molecular weight batches (PLGA 50:50, PLGA 85:15, and PLA) with higher percentages of hydrophobic impurity formation (ie, 40%, 26%, and 10%, respectively). In addition, in PBS, the high molecular weight PLGA 50:50 microspheres showed only 20% drug release with ~66% mean impurity content. The chemically modified peptide impurities inside microspheres were structurally confirmed through Fourier transform-mass spectrometry (FT-MS) and liquid chromatography/mass spectrometry (LC-MS/MS) analyses after extraction procedures. The adduct compounds were identified as covalently modified conjugates of octreotide with lactic and glycolic acid mono-

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Section: In Vitro Release In Acetate and Phosphate Buffer Systemsmentioning

confidence: 99%

Identification of chemically modified peptide from poly(D,L-lactide-co-glycolide) microspheres under in vitro release conditions

et al. 2003

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“…[1][2][3][4][5][6] Mucoadhesive polymers may fulfill the desirable features of a prolonged residence time at the site of drug absorption owing to increased contact with the absorbing mucosa, resulting in a steep concentration gradient to favor drug absorption, and localization in specified regions to improve and enhance the bioavailability of the drug. 7 Factors such as cross-linking status, ionic modification, and salt formation can significantly influence the ability of a material to show substantial mucoadhesion in an in vitro system.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods

2004

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The mucoadhesive properties of chitosan microspheres prepared by different methods were evaluated by studying the interaction between mucin and microspheres in aqueous solution. The interaction was determined by the measurement of mucin adsorbed on the microspheres. A strong interaction between chitosan microspheres and mucin was detected. The intensity of the interaction was dependent upon the method of preparation of chitosan microspheres and the amount of mucin added. The extent of mucus adsorption was proportional to the absolute values of the positive zeta potential of chitosan microspheres. The zeta potential in turn was found to be dependent upon the method of preparation of microspheres. The adsorption of type III mucin (1% sialic acid content) was interpreted using Freundlich or Langmuir adsorption isotherms. The values of r 2 were greater for Langmuir isotherm as compared with Freundlich isotherm. The adsorption of a suspension of chitosan microspheres in the rat small intestine indicated that chitosan microspheres prepared by tripolyphosphate cross-linking and emulsification ionotropic gelation can be used as an excellent mucoadhesive delivery system. The microspheres prepared by glutaraldehyde and thermal cross-linking showed good stability in HCl as compared with microspheres prepared by tripolyphosphate and emulsification ionotropic gelation.

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“…A previously described dialysis technique was used to determine the in vitro release from Orntide microspheres [27]. Approximately 20 mg of the microspheres were quantitatively transferred to a 7 mL dialysis tube (Tube-O-Dilalyzer; MWCO, 300 000 Da) containing 5.0 mL of AB, which in turn was placed in a 50 mL tube containing 40 mL of the same release medium.…”

Section: In Vitro Release Studymentioning

confidence: 99%

Evaluation of orntide microspheres in a rat animal model and correlation to in vitro release profiles

et al. 2000

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Orntide acetate, a novel luteinizing hormone-releasing hormone (LHRH) antagonist, was prepared and evaluated in vivo in 30-day and 120-day sustained delivery formulations using a rat animal model. Orntide poly(d,l-lactide-co-glycolide) (PLGA) and poly(d,l-lactide) (PLA) microspheres were prepared by a dispersion method and administered subcutaneously in a liquid vehicle to rats at 2.2 mg Orntide/kg of body weight (30-day forms) or 8.8 mg Orntide/kg (120-day forms). Serum levels of Orntide and testosterone were monitored by radioimmunoassays, and a dose-response study at 4 doses (3, 2.25, 1.5, and 1.75 mg Orntide/kg) was conducted to determine the effective dose of Orntide. Microspheres with diameters between 3.9 and 14 µ were prepared. The onset and duration of testosterone suppression varied for different microsphere formulations and were influenced both by polymer properties and by microsphere characteristics. Microspheres prepared with 50:50 and 75:25 copolymers effectively sustained peptide release for 14 to 28 days, whereas an 85:15 copolymer and the PLA microspheres extended the pharmacological response for more than 120 days. Increase in drug load generally accelerated peptide release from the microspheres, resulting in higher initial serum levels of Orntide and shorter duration of the release. In general, apparent release was faster in vivo than under in vitro conditions. Orntide microspheres effectively suppressed testosterone in rats, providing rapid onset of release and extended periods of chemical castration. Testosterone suppression occurred immediately after microsphere administration without the initial elevation seen with LHRH superagonists.

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A novelin vitro release technique for peptide-containing biodegradable microspheres

Cited by 18 publications

References 29 publications

Identification of chemically modified peptide from poly(D,L-lactide-co-glycolide) microspheres under in vitro release conditions

Identification of chemically modified peptide from poly(D,L-lactide-co-glycolide) microspheres under in vitro release conditions

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods

Evaluation of orntide microspheres in a rat animal model and correlation to in vitro release profiles

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