ANALYSIS AND MODELING OF DICLOFENAC SODIUM RELEASE KINETICS FROM HPMC TABLETS
Multi-scale and/or multi-disciplinary approach to process-product innovation
Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2)
Keywords: controlled release of drug, hydrogels, diclofenac sodium, swelling, diffusion.
Anna Angela Barba1*, Matteo d’Amore1, Gaetano Lamberti2,
1Dipartimento di Scienze Farmaceutiche, Università di Salerno,
2 Dipartimento di Ingegneria Chimica e Alimentare, Università di Salerno,
Via Ponte Don Melillo - 84084 Fisciano (SA) ITALY
*aabarba@unisa.it - tel. +39 089969240 fax +39 089969602
Controlled drug delivery is a key topic in pharmacology and many researchers all over the world are currently involved in related studies. The behaviors of pharmaceutical systems are dominated by mass transport phenomena, which can be described by methodologies typical of chemical and processes engineering. The proper description of these systems is very important in pharmaceutical systems design and drug delivery testing.
In this work the release kinetics of DS (diclofenac sodium, a NSAID, non-steroidal anti-inflammatory drug) from tablets made of DF and of HPMC (hydroxypropylmethylcellulose, an hydrogels which swells in presence of water or physiological fluids) was investigated. Tablets were made by compressing HPMC and DS powders, previously weighted and mixed in the ratio 67% HPMC / 33% DF, with a tabletting machine having a 13 mm flat-faced punch, applying a force of 50 kN for 5 minutes. All tablets, shaped as discs, were 13 mm in diameter and up to 2 mm in thickness and were made up of 300 mg of HPMC/DF mixture.
The tablets were dissolved in USP XXVIII apparatus 2, (AT7 Smart, Sotax). Each tablet was immersed in 900 mL of distilled water kept at 37°C, mixed by paddle rotating at 100 rpm. At given time intervals, the DS concentration in each vessel was assayed by an UV-visible spectrophotometer (Lambda 25, Perkin Elmer) working at a wavelength of 275 nm. The dissolution apparatus and the spectrophotometer were connected by a peristaltic pump, which avoids the need for periodic withdrawn/replacements of sample from the vessels. Furthermore, at a given time, tablets were extracted from the vessels, carefully weighed, dried, weighed once more and completely dissolved in distilled water to assay the unreleased drug. Thus, the traditional release profile was obtained in term of fractional release versus time, and also the polymer, the drug and the water mass in the swelling device were determined as functions of time.
These last data (the masses evolutions) served as basis for the tuning of a physical model able to describe the water up-take by diffusion in the tablet, the swelling of the system, the drug diffusion toward the external medium (which causes the drug release) and the polymer erosion. Finally, the model was checked by comparing with the experimental release profile, showing a good agreement.
Presented Tuesday 18, 12:00 to 12:20, in session Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2).
