1. RESULTS CONCLUSIONS REFERENCES
Artificial Membrane Selection for Franz Cell Diffusion Testing of Semi-Solid Ketoconazole (KZ) Formulations
Ashmita Ramanah1, Roderick Bryan Walker1*
1Department of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown 6140
Table 2: % Recovery of KZ bound to membranes after filtration.
The highest recovery of KZ after filtration and lowest binding of the drug to the membrane were demonstrated by Silatos™ 0.13mm silicone sheeting and 0.2µm Sartorius® cellulose acetate.
Silatos™ 0.13mm silicone sheeting and 0.2µm Sartorius® cellulose acetate were chosen for preliminary studies of in-vitro release testing.
Figure 1. In-vitro release profile comparison of KZ release from a 2% w/v KZ solution. Silatos™ 0.13mm silicone sheeting versus 0.2µm Sartorius® cellulose acetate using a receptor medium of 50:50 (ethanol:pH 4.5 phosphate buffer 0.05M) (n=3).
Following analysis of data from preliminary in-vitro release testing, the 0.2µm Sartorius® cellulose acetate was selected for future Franz diffusion cell in-vitro release testing of semi-solid KZ formulations. The use of this membrane demonstrated better discrimination of KZ release over 24hours when compared to the Silatos™ 0.13mm silicone sheeting. The testing permitted discrimination between release for the 2% w/v KZ solution, Ketazol® cream and Kez® shampoo.
INTRODUCTION
Membrane selection is an important step in the development of an in-vitro release test method using Franz diffusion cells. (1)
Skin is a non-uniform and inhomogeneous membrane and involves unpredictable variations such as age, race, sex and anatomical site. (2;3)
Artificial membranes demonstrates good experimental reproducibility at a higher scale as they are inert, structurally identical, easily available and cheaper compared to skin. (1)
Vertical Franz cell diffusion system is the standard in-vitro release apparatus used for semi-solid formulations. (4)
Chosen membranes should allow not KZ to be bound to them.
Membranes should be fully permeable to a solution of KZ.
Membranes should be void of any compound that would tamper with the results of the in-vitro analysis of semi-solid KZ formulations.
Membrane chosen should demonstrate the best in-vitro release profile of semi-solid KZ formulations over 24hours.
Artificial membranes tested were 8.0µm Sartorius® cellulose nitrate, 0.8µm Sartorius® cellulose nitrate, Silatos™ 0.13mm silicone sheeting, 0.2µm Whatman® nitrocellulose, 0.025µm Millipore® nitrocellulose, 0.2µm Sartorius® cellulose acetate.
100mL of standard KZ solutions of 20µg/mL and 100µg/mL were prepared in a solution made up of 4g citric acid, 1.5g polysorbate 80, 9.5g ethanol, 85g of pH 5.0 citro-phosphate buffer.
Standard KZ solutions were passed through the synthetic membranes under vacuum filtration using an Eyela® Aspirator A-2S (Tokyo Rikakikai Co. Ltd).
Recovery of KZ was analysed using a developed and validated HPLC method.
After filtration, each membrane was further soaked into a 5mL solution that was previously used to dissolve KZ, for the evaluation of drug binding onto the membranes and sonicated using a Cole-Parmer® Ultrasonic cleaner (Chicago, Illinois, USA).
In-vitro release profiles of 2% w/v KZ solution, Ketazol® cream and Kez® shampoo were obtained using two chosen membranes through a vertical Franz cell diffusion system. A receptor medium of 50:50 (ethanol:pH 4.5 phosphate buffer 0.05M) was used.
Table 1: % Recovery of KZ from standard solutions after filtration through artificial membranes.
*The 0.025µm Millipore® nitrocellulose membrane filter did not accommodate 100mL of standard KZ solution, however the filtrate was analysed.
INTRODUCTION
Artificial membrane
20µg/mL
100µg/mL
8.0µm Sartorius® cellulose nitrate
1.18
0.8µm Sartorius® cellulose nitrate
1.12
Silatos™ 0.13mm silicone sheeting
0.84
0.2µm Whatman® nitrocellulose
0.80
*0.025µm Millipore® nitrocellulose
0.87
0.2µm Sartorius® cellulose acetate
0.81
OBJECTIVES
METHODS
RESULTS
CONCLUSIONS
Artificial membrane
20µg/mL
100µg/mL
8.0µm Sartorius® cellulose nitrate 97 94
0.8µm Sartorius® cellulose nitrate 96
Silatos™ 0.13mm silicone sheeting 98
0.2µm Whatman® nitrocellulose 91
*0.025µm Millipore® nitrocellulose
0.2µm Sartorius® cellulose acetate
REFERENCES
Kailas D Thaker, Wendy H Chern. Development and validation of in vitro release tests for semisolid dosage forms- Case Study. Dissolution Technologies , Ref Type: Journal (Full)
D Bommannan, Russell O Potts, Richard H Guy. Examination of Stratum Corneum Barrier Function In Vivo by Infrared Spectroscopy. Journal of Investigative Dermatology 95, Ref Type: Journal (Full)
Shiow-Fern Ng, Jennifer J Rouse, Gillian M Eccleston. Validation of a static Franz diffusion cell system for in vivo permeation studies. AAPS PharmSciTech 11[3], Ref Type: Journal (Full)
Wilna Liebenberg, Eileen Engelbrecht, Anita Wessels, Bharathi Devarakonda, Wenzhan Yang, Melgardt M.De Villiers. A Comparative Study of the Release of Active Ingredients
from Semisolid Cosmeceuticals Measured with Franz, Enhancer or Flow-Through Cell Diffusion Apparatus. Journal of Food and Drug Analysis 12[1], Ref Type: Journal (Full)
Acknowledgements: The authors are grateful for the financial support from the Rhodes University Research Committee(RBW). Presented at The Academy of Pharmaceutical Sciences of South Africa, Cape Town, October 2013.