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In Vitro Release Test Method for Evaluation of Clotrimazole Nail Lacquers
Written by V. Nalamothu, R.J. Wigent and J.B. Schwartz   

 

Abstract

Medicinal nail lacquer is a unique dosage form manufactured as a topical solution forming a dry film after application to the nail. In vitro release test (IVRT) is an appropriate performance test that measures the release of the drug from the polymer matrix (dried film).

A Franz Diffusion Cell System was used with a standard sample assembly to mount synthetic membranes. Optimum conditions were developed to provide an infinite sink for the drug to diffuse through the membranes. Nail lacquer was applied onto the synthetic membrane and the drug release from dried lacquer films was assessed by HPLC for drug content.

The developed IVRT method demonstrated a dose-related drug release (12%>8%>4%) with correlation to √t . The developed IVRT method also differentiated the concentration of a polymer (20%>30%>10%) and concentration of tail solvent (8%~5%>2%) and their effect on the drug release.

The developed method using the conventional Franz diffusion system can differentiate formulations with variable composition of different ingredient(s) and drug concentrations.

Objectives

  • To develop a performance test method that can differentiate clotrimazole nail lacquer formulations with variable composition of different ingredients and drug concentrations.
  • To systematically investigate the effect of key excipient(s) on the drug release from dried nail lacquer film
  • To demonstrate the relationship of formulation variables on the release rate of clotrimazole

Methods

A Logan-Hitachi 912 Automated Transdermal IVRT system (Logan Instruments Corp., Somerset, NJ) with a standard sample assembly was used. The receiving medium used in all In Vitro Release Test Method for Evaluation of Clotrimazole Nail Lacquersthe studies consisted of ethanolic phosphate buffer (pH 7.4) maintained at 370.5C. These conditions provided an infinite sink for the drug to diffuse through the membranes.

A Logan-Hitachi 912 Automated Transdermal IVRT system (Logan Instruments Corp., Somerset, NJ) with a standard sample assembly was used. The receiving medium used in all the studies consisted of ethanolic phosphate buffer (pH 7.4) maintained at 370.5C. These conditions provided an infinite sink for the drug to diffuse through the membranes.

Nail lacquer was applied onto the synthetic membrane and allowed to dry before the membranes were mounted on the cells, and the rates of drug release from dried lacquer films were assessed. Samples of the receiving medium were taken at periodic time intervals and were analyzed by HPLC for drug content. The following equation was used to calculate the amount (Q) released.

In Vitro Release Test Method for Evaluation of Clotrimazole Nail Lacquers

 

Results

As the alcoholic content of the receptor media was increased, the drug release rate also increased. The optimal concentration of alcohol was found to be 40%v/v for the evaluation of nail lacquer formulations.

Ingredient

 1

 3

 5

 6

 7

 10

Clotrimazole

 4.00

 8.00

 12.00

8.00 

 8.00

 8.00

 8.00

 8.00

 12.00

Polymer

 30.00

 30.00

 30.00

 10.00

 20.00

 30.00

 30.00

30.00 

 30.00

 Poropylene Glycol

 2.00

  2.00

  2.00

  2.00

  2.00

 5.00

 8.00

 0.00

 10.00

 Ethyl Acetate

 17.00

 17.00

 17.00

 17.00

 17.00

 17.00

 17.00

 17.00

 17.00

 Ethyl Alcohol (200proof, SD40B)

 47.00

 43.00

 39.00

 63.00

 53.00

 40.00

 37.00

 45.00

 31.00

 

 100.00

 100.00

 100.00

 100.00

 100.00

 100.00

 100.00

 100.00

 100.00

The developed IVRT method demonstrated a dose-related drug release (12%>8%>4%; Fig. 1) with correlation to √t . The developed IVRT method also differentiated the concentration of a polymer (20%>30%>10%) and concentration of tail solvent (8%~5%>2%~0%) and their effect on the drug release

Conclusion

The developed method using the conventional Franz diffusion system can differentiate formulations with variable composition of different ingredient(s) and drug concentrations. Using this method, the effect of key excipient(s) on the drug release from the dried nail lacquer film was systematically investigated. The release studies of clotrimazole nail lacquers indicate that release rate is a function of formulation variables.

The developed method using the conventional Franz diffusion system can differentiate formulations with variable composition of different ingredient(s) and drug concentrations. Using this method, the effect of key excipient(s) on the drug release from the dried nail lacquer film was systematically investigated. The release studies of clotrimazole nail lacquers indicate that release rate is a function of formulation variables.

The developed method using the conventional Franz diffusion system can differentiate formulations with variable composition of different ingredient(s) and drug concentrations. Using this method, the effect of key excipient(s) on the drug release from the dried nail lacquer film was systematically investigated. The release studies of clotrimazole nail lacquers indicate that release rate is a function of formulation variables.

The developed method using the conventional Franz diffusion system can differentiate formulations with variable composition of different ingredient(s) and drug concentrations. Using this method, the effect of key excipient(s) on the drug release from the dried nail lacquer film was systematically investigated. The release studies of clotrimazole nail lacquers indicate that release rate is a function of formulation variables.

References

  1. Shah V.P., Elkins Siewert M., Shah V.P., “FIP/AAPS Guidelines for Dissolution/In Vitro Release Testing of Novel/Special Dosage Forms”. Dissolution Technologies, Vol.10, Issue 1, February 2003.
  2. J.S., Williams R.L. “Evaluation of the test system used for in vitro release of drugs from topical dermatological drug products”. Pharm Develop Technol. 1999;4:377-385.
  3. FDA Guidance for Industry: SUPAC-SS Nonsterile Semisolid Dosage Forms.
  4. Fares H.M., Zatz J.L. “Measurement of drug release from topical gels using two types of apparatus”. Pharm Tech. 1995;19(1):52-58.
  5. Shah V.P., Elkins J.S. “In vitro release from corticosteroid ointments”. J Pharm Sci. 1995;84:1139
  6. Higuchi, W.I. “Analysis of data on medicament release from ointments”. J Pharm Sci. 1962;51:802-804 7. Flynn G.L., Shah V.P., Tenjarla S.N., et al. “Assessment of value and applications of in vitro testing of topical dermatological drug products. Pharm Res. 1999;16:1325-1330.
 
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