Document Detail

Stable bioavailability of cyclosporin A, regardless of food intake, from soft gelatin capsules containing a new self-nanoemulsifying formulation.
MedLine Citation:
PMID:  16724578     Owner:  NLM     Status:  MEDLINE    
AIM: We recently succeeded in preparing soft gelatin capsules containing a new self-nanoemulsifying formulation consisting of cyclosporin A (CsA), triacetin, polyoxyl 40 hydrogenated castor oil, polysorbate 20, medium chain triglycerides and medium chain mono- and diglycerides. The soft capsules containing the new formulation exhibited a significantly improved physical stability in terms of the appearance of the gelatin capsule shells and the composition of the fill mass during long-term storage, compared to commercially available soft capsules containing CsA, in which ethanol was employed as a cosolvent of CsA. In the present study, the influence of a fat-rich meal on the bioavailability of CsA from the soft capsule containing the new formulation (test drug) was evaluated and the results compared to those obtained with a representative soft capsule of CsA. VOLUNTEERS AND METHODS: A randomized, open-label, 3-way crossover study was performed in the test capsules and reference soft capsules, in a fasted state or after a fat-rich breakfast. 18 healthy male volunteers received a single dose of the reference formulation (Neoral, Novartis AG, Basel, Switzerland) or test formulation (2 capsules each, 200 mg as CsA) with 240 ml of water with a 1-week washout period between the treatments, after a fat-rich (670 kcal, 45 g fat) breakfast (for the test drug, Treatment A; for the reference drug, Treatment B) or a 12-h fasting (for the test drug, Treatment C). Serial blood samples, collected over a 24-h period after the administration, were assayed for blood CsA concentrations using a specific monoclonal radioimmunoassay. RESULTS: The differences in bioavailability parameters (i.e., AUC(0-24h), AUC(0-infinity) and C(max)) between the treatments were within the range of 80-125% of the reference treatment. An analysis of variance (ANOVA) revealed no significant differences (p > 0.05) between subjects, formulations or periods. The 90% confidence intervals (CI) indicated that the differences between the treatments (Treatments A and B, Treatments A and C) were also within the criteria. CONCLUSION: These results indicate that the bioavailability of CsA from the test drug is equivalent to reference in the fed state, and is likely to be less influenced by a fat-rich meal. Therefore, the new formulation of CsA using triacetin appears to have an advantage over the commercial soft capsules of CsA using a volatile cosolvent such as ethanol.
S G Yang; D D Kim; S J Chung; C K Shim
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  44     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-26     Completed Date:  2007-07-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  233-9     Citation Subset:  IM    
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Korea.
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MeSH Terms
Administration, Oral
Biological Availability
Chemistry, Pharmaceutical
Cyclosporine / administration & dosage,  blood,  pharmacokinetics*
Dietary Fats / administration & dosage
Fasting / blood
Immunosuppressive Agents / administration & dosage,  blood,  pharmacokinetics*
Triacetin / chemistry*
Reg. No./Substance:
0/Capsules; 0/Dietary Fats; 0/Emulsions; 0/Immunosuppressive Agents; 102-76-1/Triacetin; 59865-13-3/Cyclosporine; 9000-70-8/Gelatin

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