ABSTRACT
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.
ABSTRACT
Aim: To investigate interpolymer complexes (IPCs) formation between carbopol and cationic polymers such as chitosan and Eudragit E for oral controlled drug delivery systems. Methodology: The prepared IPCs were investigated using Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Chitosan-carbopol and Eudragit E-carbopol IPCs loaded with diltiazem hydrochloride (DTZ HCl) with different drug:polymer ratios were also prepared. Diltiazem hydrochloride tablets were prepared using polymers alone, physical mixtures of chitosan or Eudragit E with carbopol and the corresponding drug loaded IPCs. In-vitro release studies were carried out in two dissolution media; 0.1 NHCl of pH 1.2 and phosphate buffer of pH 7.4. Results: The dissolution rate of DTZ HCl from the prepared tablets were found to be dependant on the interaction between chitosan or Eudragit E with carbopol in the physical mixture, drug:polymer ratio and pH of the dissolution medium. Tablets prepared using chitosan – carbopol IPC, Eudragit E – carbopol IPC, and Eudragit E – carbopol physical mixture of drug:polymer ratio 1:5 were selected for the in-vivo study using rabbits. The results showed a lower peak plasma concentration and marked prolonged release effect of tablets containing Eudragit E – carbopol IPC and the corresponding physical mixture compared to that of commercial Altiazem tablets. Conclusion: Tablets containing Eudragit E – carbopol or chitosan – carbopol physical mixtures showed prolonged drug release compared to that containing the corresponding IPCs, Furthermore, Eudragit E- carbopol matrix tablets showed slower drug release than that of chitosan – carbopol