Document Detail


Examination of the impact of a range of Pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquone.
MedLine Citation:
PMID:  16734982     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exogenous surfactants are increasingly used to enhance the dispersion properties of lipid-based formulations of poorly water-soluble drugs, yet their possible effects on formulation digestion and oral bioavailability in-vivo are not well documented. In this study, in-vitro dispersion and digestion experiments were conducted using formulations comprising a blend of long-chain glycerides, ethanol, a model poorly water-soluble drug (atovaquone), and a series of surfactants including Cremophor EL and a range of Pluronic surfactants (Pluronics L121, L61, L72, L43 and F68). Inclusion of Cremophor EL, a surfactant with a high hydrophilic-lipophilic balance (HLB), promoted complete digestion of the formulation and effective dispersion and solubilisation of the lipolytic products and co-administered drug. Surprisingly, formulations containing the Pluronic (L121) with the lowest HLB (0.5) equally effectively promoted digestion and drug solubilisation and a trend towards decreased digestion and drug solubilisation was observed with Pluronics of increasing HLB values. All formulations effectively prevented drug precipitation, suggesting possible utility in-vivo, and no correlation was evident between the ability of the formulations to self-emulsify on dispersion and to promote drug solubilisation on digestion. Subsequent assessment of the oral bioavailability of atovaquone after administration of formulations containing Cremophor EL or Pluronic L121 or a simple solution of atovaquone in long-chain glycerides confirmed the utility of lipid-based formulations for enhancing the oral bioavailability of poorly water-soluble drugs such as atovaquone, but also indicated that in some cases microemulsion preconcentrate formulations may not provide additional bioavailability benefits beyond that achievable using simple lipid solutions.
Authors:
Leab Sek; Ben J Boyd; William N Charman; Christopher J H Porter
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  58     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-31     Completed Date:  2006-09-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  809-20     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Atovaquone
Biological Availability
Chemistry, Pharmaceutical
Dogs
Glycerides / metabolism
Male
Naphthoquinones / administration & dosage*,  chemistry,  pharmacokinetics*
Particle Size
Poloxamer / administration & dosage*
Polyethylene Glycols / administration & dosage
Solubility
Surface-Active Agents / administration & dosage*
Chemical
Reg. No./Substance:
0/Glycerides; 0/Naphthoquinones; 0/Polyethylene Glycols; 0/Surface-Active Agents; 106392-12-5/Poloxamer; 39279-69-1/cremophor; 94015-53-9/Atovaquone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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