Formulation and Evaluation of Gel Forming Ocular Minitablets Containing Piroxicam

Aims: The purpose of this in vitro and ex vivo study was to prepare and characterise ocular minitablets of piroxicam based on different polymeric matrices and to evaluate their potential to provide prolonged and controlled drug release to ocular tissues after surface administration.
Study Design: Experimental study and ex-vivo study.
Place and Duration of Study: School of Pharmacy, University of East Anglia, Norwich, Norfolk, UK, between July 2011 and March 2012.
Methodology: A range of placebo minitablet formulations were prepared based on pharmaceutically-acceptable polymers of differing chemical and physical properties. These were evaluated using standard physical and visual imaging methods. A subset of placebo formulations was chosen to prepare medicated minitablets containing 5 %w/w piroxicam as a model drug. Three different in vitro methodologies were used to assess drug release from the minitablets. An ex vivo porcine ocular method was used to assess likely tissue distribution of the drug after surface ocular administration of the minitablets.
Results: Minitablets were successfully produced from all formulations. The in vitro drug release profile was dependent on the chemistry of the polymer used, its hydration and swelling behaviour and to some extent, the methodology used for assessing the drug release profile. The ex vivo studies in porcine eyes suggested that the drug disposition was inversely related to the hydration and swelling behaviour of the polymer. Minitablets containing piroxicam based on Pluronic F127 showed the highest posterior segment ocular bioavailability of the formulations studied in the ex vivo model. Conversely, the more highly swelling minitablet formulations showed higher anterior segment bioavailability.
Conclusions: Ocular minitablets containing 5 %w/w piroxicam were successfully produced from a range of polymer matrices. In vitro release was shown to be dependent on the physical and chemical properties of the polymers used as the basis of the minitablets. Posterior segment deposition in an ex vivo model was greatest in the formulation which showed limited hydration and swelling behaviour in a simulated ocular environment.