Investigation on the Use of Dialysis Membrane on Drug Release from Micro Particles in Compendial Apparatus 1 and 3

Purpose To study the effect of the properties of dialysis membrane in terms of the molecular weight cut-off (MWCO) and the surface area, and the effect of hydrodynamics on release of microparticle compounds represented as suspensions for oral administration, in order to develop a compendial release test for products containing micro and nano particles. Methods Release of paracetamol (120mg/5ml) and ibuprofen (100mg/5ml) from suspensions for oral administration was tested in phosphate buffer pH 6.8 and of carbamazepine (100 mg/5 ml) from suspension for oral administration in 1% SLS. Three different MWCO biotech grade cellulose ester membranes (Float-A-Lyzer) were used: 0.1-0.5 kD, 0.5-1 kD, 3.5-5 kD. Dialysis membranes were placed with the use of a special adaptor made from Agilent in USP Apparatus 1 (100rpm) and USP Apparatus 3 (15 dpm, 30 dpm, 45 dpm). One (2.5 mL) or two different (2.5 mL and 5 mL) doses were placed in the Float-A-Lyzer and samples were withdrawn at regular time intervals. Each suspension was also tested as a free suspension in USP Apparatus 1 at 100rpm. The amount of drug released in all cases was determined with UV. All experiments were performed in triplicates. Results Release of the drug from the suspension in the dialysis membrane was slower than from the free suspension in all cases. The increase in the MWCO leads to an increase in release and drugs with high solubility released faster, whereas for poorly soluble drugs a lag time in release is observed which is followed by an exponential increase as diffusion through the membrane is limited by the dissolution of the drug molecule inside the membrane. The effect of the surface area of the membrane on release was minimal. A higher release was observed for higher dip rates in USP Apparatus 3, and release was comparable for USP Apparatus 1 (100rpm) and 3 (30 dpm). Conclusion The use of Float-A-Lyzer for release testing of suspensions proves the feasibility of utilizing dialysis membranes, with controlled surface area and MWCO, by providing consistency in sample introduction and accurate results that would be needed for a product containing micro and nano particles for product development as well as routine QC performance testing.