Bioequivalence of different prednisolone tablet formulations

Department of Pharmacology, University of Tübingen, Germany.
Arzneimittel-Forschung (Impact Factor: 0.7). 02/2001; 51(8):638-42. DOI: 10.1055/s-0031-1300094
Source: PubMed


The relative bioavailability of different prednisolone (CAS 50-24-8) tablet formulations (Prednisolon Ferring 2, 5, and 20 mg) was investigated in comparison to a reference formulation. The study was performed in a GCP/ICH-conform manner using a randomized cross-over design in 13 healthy volunteers. With respect to the pharmacokinetic parameters Cmax (maximal prednisolone concentration), AUC0-12 h (area under the concentration-time curve until 12 h after drug intake), AUC0-infinity (area under the concentration-time curve until infinity), and t1/2 (elimination half-life time), 10 x 2 mg prednisolone tablets did not show any relevant differences as compared to the reference (1 x 20 mg) meaning that the 90% confidence intervals were within the given 0.80-1.25 limits for the decision of bioequivalence. Although not statistically significant, tmax (time to reach the maximal prednisolone plasma concentration) was 11 min shorter regarding the test preparation as compared to the reference. The pharmacokinetic parameters of 4 x 5 prednisolone tablets were also well in accordance with the reference. The most important parameters Cmax, AUC and t1/2 were within the defined limits for the acceptance of bioequivalence and, in addition, tmax did not show any significant differences. The 20 mg prednisolone tablet formulation showed almost identical parameters of Cmax, AUC, t1/2 und tmax in comparison to the reference substance. Taken together, the results of the bioavailability parameters indicate the bioequivalence of the three prednisolone test preparations as compared to the reference.

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    ABSTRACT: Two prednisolone (CAS 50-24-8) formulations (Prednisolone 50 mg Ferring tablets as the test preparation and tablets of a reference preparation) were investigated in 13 healthy volunteers in order to prove bioequivalence between these preparations. A single oral dose of 50 mg was given using a randomized, two-way cross-over design with a wash-out period of one week. Blood samples for determination of prednisolone plasma concentrations were collected up to 15 h following drug administration. Additionally, in vitro tests were performed with tablets from the same lots to determine dissolution characteristics. Prednisolone concentrations were measured by means of validated HPLC with UV-detection. Maximum concentrations (Cmax) of 1020.9 +/- 57.8 and 1053.3 +/- 55.7 ng/ml were achieved for the test and the reference preparation, respectively. The AUC0-infinity was 212.2 +/- 13.2 micrograms.min/ml (test preparation) and 222.2 +/- 14.3 micrograms.min/ml (reference preparation). The 90% confidence intervals of the test to reference ratios were within the range of 80-125% with 97.8-101.3% for Cmax and 98.1-100.4% for AUC0-infinity. The time to reach maximum plasma concentration (tmax) tended to be lower (-25%) in the test (39.6 +/- 6.4 min) as compared to the reference preparation (52.8 +/- 9.0 min). Interestingly, this difference correlated well with the observation of a more rapid dissolution rate of the test preparation by some 10 min. Both prednisolone formulations were well tolerated. Based on the results obtained in this study, (1) bioequivalence between the test and the reference preparation was clearly demonstrated and (2) a positive correlation between dissolution rate observed in vitro and tmax as measured in vivo was found.
    Arzneimittel-Forschung 12/2001; 51(11):911-5. DOI:10.1055/s-0031-1300136 · 0.70 Impact Factor
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    ABSTRACT: A 47-year-old woman received combination therapy with prednisolone (PSL), danazol, cepharanthin, ascorbic acid, and cimetidine for the treatment of idiopathic thrombocytopenic purpura. The platelet count was well controlled for over 1 year. Then the PSL tablet formulation was altered from Tablet A to Tablet B with the same treatment regimen, but the platelet counts fell drastically thereafter. However, the platelet counts recovered by changing the PSL tablet formulation back from Tablet B to Tablet A. In vitro dissolution testing was undertaken to assess bioequivalence between Tablet A and Tablet B. PSL in Tablet B was released more slowly compared with that in Tablet A regardless of the medium pH conditions, and the difference in the release rate between the two tablet formulations increased with increasing medium pH value. The difference exceeded the allowance limit (15%) for judgment of bioequivalence under conditions above pH 4, indicating that Tablet A and Tablet B might be nonbioequivalent. The intragastric pH of the patient was probably raised due to coadministration of cimetidine. Therefore the present results suggest that the disparity in the immunosuppressive effects between the two PSL tablet formulations was attributable to the difference in their dissolution behavior in the gastrointestinal tract. We consider that it is better to avoid interchanging PSL tablet formulations in clinical practice.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 11/2002; 122(10):813-7. DOI:10.1248/yakushi.122.813 · 0.26 Impact Factor
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    ABSTRACT: Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks.
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