Document Detail


Evaluation of the in vitro and in vivo performance of two sustained-release lithium carbonate matrix tablets. Effect of different diets on the bioavailability.
MedLine Citation:
PMID:  10065346     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two sustained-release (SR) lithium carbonate (Li) matrix tablets, which use a hydrophilic (HP) matrix of hydroxypropylmethylcellulose (Methocel 4K MP) and a lipid (L) matrix of hydrogenated castor oil (Cutina HR) as sustaining agents, have been studied. In vitro performance through dissolution tests in different media was established. The L and HP formulations were affected by the composition of the dissolution media, and liberation was complete in 8 hr using a variable-pH medium that simulates the gastrointestinal (Gl) pH. Liberation was better described by the diffusional model of the square root of time for the L matrix and by zero-order kinetics for the HP matrix. Absolute bioavailability (BA) and food-induced changes on BA of both formulations were studied. The in vivo study design was a 4 x 4 Latin square involving 12 subjects who received two tablets of a 300-mg dose of SR formulations while fasting or with a standardized normal, high-fat, or high-fat/high-protein meal. The results for both formulations showed no differences in the disposition parameters and mean residence time when the tablets were administered with any type of diet. Changes in rate of absorption were found when both types of tablets were administered with any class of diet. The analysis of the ratio Cmax/AUC (area under the curve) evidenced that changes in Cmax were attributable to a higher rate of absorption for the HP matrix and to a higher amount absorbed for the L matrix. In the last, high-fat and high-fat/high-protein diets produced higher AUCs than under fasting condition. The SR Li tablets formulated with hydrogenated castor oil were affected more by high-fat food, probably because of the increase of pancreatic and biliary secretions promoted by the meal, which would affect the matrix itself. The HP matrix was also affected, but to a lesser extent. The magnitude of the change in Cmax observed with this matrix probably is not important from a clinical point of view. Absolute BA was very low for the lipid matrix; in addition, since it is more seriously affected by food, probably it is not a good choice for a drug such as lithium. The in vivo behavior of the HP matrix makes it advisable to invest in efforts to achieve increased BA. Comparing in vitro and in vivo results, the focus should be achieving sustained, but complete, in vitro liberation in not more than 3 hr, with simulation of the transit time through the stomach and small bowel since lithium ion is only absorbed to this point.
Authors:
M N Gai; S Ferj; E García; C Seitz; A M Thielemann; M T Andonaegui
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug development and industrial pharmacy     Volume:  25     ISSN:  0363-9045     ISO Abbreviation:  Drug Dev Ind Pharm     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-05-06     Completed Date:  1999-05-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7802620     Medline TA:  Drug Dev Ind Pharm     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  131-40     Citation Subset:  IM    
Affiliation:
Department of Science and Pharmaceutical Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Antidepressive Agents / blood,  pharmacokinetics*,  urine
Biological Availability
Chemistry, Pharmaceutical
Cross-Over Studies
Delayed-Action Preparations
Dietary Fats / pharmacology*
Dietary Proteins / pharmacology*
Fasting / metabolism
Gastric Mucosa / drug effects
Humans
Hydrogen-Ion Concentration
Lithium Carbonate / blood,  pharmacokinetics*,  urine
Male
Tablets
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Delayed-Action Preparations; 0/Dietary Fats; 0/Dietary Proteins; 0/Tablets; 554-13-2/Lithium Carbonate

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


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