Validation of USP apparatus 4 method for microsphere in vitro release testing using Risperdal® Consta®

Rawat, Archana; Stippler, Erika; Shah, Vinod P.; Burgess, Diane J.

doi:10.1016/j.ijpharm.2011.08.035

Cited by 58 publications

(22 citation statements)

References 17 publications

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“…1). Indeed, in risperidone 65:35 microspheres, the degradation behavior of PLGA proceeded with an initial rapid decrease in Mw (ΔMw≈50% during the first 5 days), probably occurring at very early stages (e.g., 24 h), followed by a more gradual loss in molecular weight (11). In risperidone 85:15 microspheres, the same Mw reduction was not observed until 15 days of incubation.…”

Section: Resultsmentioning

confidence: 95%

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Accelerated Polymer Biodegradation of Risperidone Poly(d, l-Lactide-Co-Glycolide) Microspheres

2012

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Abstract. The influence of a tertiary amine, namely risperidone (pKa07.9) on the degradation of poly(D, L lactide-co-glycolide) (PLGA) microspheres was elucidated. Risperidone and blank microspheres were fabricated at two lactide/glycolide ratios, 65:35 and 85:15. The microspheres were characterized for drug loading by high-performance liquid chromatography, particle size by laser diffractometry, and surface morphology by scanning electron microscopy. Polymer degradation studies were carried out with drugloaded microspheres and blank microspheres in presence of free risperidone in 0.02 M PBS containing 0.02% Tween®80 at 37°C. Molecular weight was monitored by gel permeation chromatography. Risperidone and blank microspheres had similar size distribution and were spherical with a relatively nonporous smooth surface. The presence of risperidone within the microspheres enhanced the hydrolytic degradation in both polymeric matrices with faster degradation occurring in 65:35 PLGA. The molecular weight decreased according to pseudo-first-order kinetics for all the formulations. During the degradation study, the surface morphology of drug-loaded microspheres was affected by the presence of risperidone and resulted in shriveled microspheres in which there appeared to be an intrabatch variation with the larger microspheres being less shriveled than the smaller ones. When blank microspheres were incubated in free risperidone solutions, a concentration-dependent effect on the development of surface porosity could be observed. Risperidone accelerates the hydrolytic degradation of PLGA, presumably within the microenvironment of the drug-loaded particles, and this phenomenon must be taken into consideration in designing PLGA dosage forms of tertiary amine drugs.

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Section: Resultsmentioning

confidence: 95%

“…Early stages polymer degradation has been observed and ascribed to risperidone. Nevertheless, degradation studies were performed in non physiological temperature conditions (40°C and 45°C) and simply for the first 4 days acquiring an imperfect picture of the phenomenon (11).…”

Section: Introductionmentioning

confidence: 99%

Accelerated Polymer Biodegradation of Risperidone Poly(d, l-Lactide-Co-Glycolide) Microspheres

2012

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“…Fresh media (0.9 ml) were mixed with pellets (if any) and transferred back to the testing vessels. In case of the USP apparatus 4 method, a previously developed and validated USP apparatus 4 method was used [24]. Briefly, the microspheres (10 mg) were mixed with glass beads (1 mm) and placed in USP apparatus 4 dissolution cells.…”

Section: In Vitro Release Studiesmentioning

confidence: 99%

“…Various methods (e.g. sample-and-separate, membrane dialysis, and continuous flow (USP apparatus 4)) are commonly used for in vitro release testing of parenteral microspheres [24,[28][29][30][31]. However, the procedures and apparatus used vary among laboratories, and this makes inter-laboratory comparisons difficult.…”

Section: In Vitro Release Studies Of Risperidone Microspheresmentioning

confidence: 99%

In vitro-in vivo correlation of parenteral risperidone polymeric microspheres

Shen

Choi

et al. 2015

Journal of Controlled Release

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The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but prepared with different manufacturing processes. Risperidone was chosen as a model therapeutic and poly(lactic-co-glycolic acid) (PLGA) with similar molecular weight as that used in the commercial product Risperdal ® Consta ® was used to prepare risperidone microspheres. Various manufacturing processes were investigated to produce the risperidone microspheres with similar drug loading (approx. 37%) but distinctly different physicochemical properties (e.g. porosity, particle size and particle size distribution). In vitro release of the risperidone microspheres was investigated using different release testing methods (such as sampleand-separate and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone microsphere formulations following intramuscular administration were determined using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were deconvoluted using the LooRiegelman method and the calculated in vivo release was compared with the in vitro release of these microspheres. Level A IVIVCs were established and validated for the compositionally equivalent risperidone microspheres based on the in vitro release data obtained using USP apparatus 4. The developed IVIVCs demonstrated good predictability and were robust. These results showed that the developed USP apparatus 4 method was capable of discriminating PLGA microspheres that are equivalent in formulation composition but with manufacturing differences and predicting their in vivo performance in the investigated animal model.

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“…The microspheres dispersed with the glass beads are packed in the flow-through cells. This modification of the flowthrough cell is useful in minimizing aggregation of microspheres and separating them from the release media (9,10).…”

Section: Microspheresmentioning

confidence: 99%

Performance Test for Parenteral Dosage Forms

Shah¹,

DeMuth²,

Hunt³

2015

Dissolution Technol.

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Procedures and acceptance criteria for testing parenteral drug products are divided into two categories: (1) those that assess product quality attributes (e.g., identification, sterility, and particulate matter) and are contained in general chapter Injections and Implanted Drug Products <1>; and (2) those that assess product performance (e.g., in vitro release of the drug substance from the drug product). A product performance test (i.e., drug release test) should be carried out using appropriate test parameters and procedures. This Stimuli article addresses performance tests for parenteral drug products and the various methodologies.

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Validation of USP apparatus 4 method for microsphere in vitro release testing using Risperdal® Consta®

Cited by 58 publications

References 17 publications

Accelerated Polymer Biodegradation of Risperidone Poly(d, l-Lactide-Co-Glycolide) Microspheres

Accelerated Polymer Biodegradation of Risperidone Poly(d, l-Lactide-Co-Glycolide) Microspheres

In vitro-in vivo correlation of parenteral risperidone polymeric microspheres

Performance Test for Parenteral Dosage Forms

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