ABSTRACT
Implantable drug delivery systems (IDDS) are useful parenteral controlled release delivery devices necessary when drug candidates have poor absorption by other routes of administration, short biological half-lives or where targeting and site specific delivery of the drug moiety is desired. The aim of this study was to develop Ibuprofen loaded implant pellets using some natural and synthetic biodegradable polymers and to evaluate the effects of formulation variables on the release profiles of the implant formulations.
Solvent casting technique was employed for the formulation of Ibuprofen loaded implant pellets using Gelatin-Sodium Alginate and Gelatin-Hydroxylprophylmethylcellulose admixtures (80:20) as the polymer blend. Glycerin was used as the plasticizing agent. Various formulation variables such as polymer type and combination, drug loading, plasticizer type and concentration as well as the inclusion of hydrophobic mass (carnauba wax) as an external coat were investigated. The cut pellets were evaluated for their physico-chemical properties such as weight uniformity, thickness, swelling index, moisture content, moisture sorption, drug content, drug-excipient interactions as well as in vitro drug release. The in vivo analgesic activity of the implants on acetic acid induced mouse writhing in mice was also determined.
The implant pellets had uniform character with minimum batch to batch variation. It was found that the results for the mean diameter/thickness of the implants (2.90 ± 0.20 to 3.05 ± 1.50 mm), mean weight variation (123 ± 10.14 to 128 ± 0.20 mg), mean percentage drug content (95.50 ± 0.40%), mean percentage moisture content (26.12 ± 0.05 to 29.94 ± 0.02%) and swelling index (3.23 ± 0.15 to 5.24 ± 0.01%) were all within satisfactory acceptable limits for biodegradable gelatinous polymers. In vitro drug release studies indicate that the implants successfully extended the release of ibuprofen over a five (5) day study period. The in vitro release profiles of the implants incorporating different types of plasticizers were observed to follow the order: Glycerin > polyethylene glycol 400 > castor oil. The release kinetics results indicate that the mechanism of drug release from the implant formulations was via Higuchi (R2 = 0.996) diffusion model. The korsmeyer and peppas (n > 0.45) result indicates that the diffusion was Non-fickian. Results from the fourier transform infrared spectroscopy (FTIR) Spectra indicates that there was no interaction between the drug and the polymers used. Moisture sorption isotherm of implant formulations under different conditions of relative humidity measured at 300C indicates that the implants causes a rapid weight gain in water (RH100%) and an appreciable weight loss in activated silica gel (RH0%) while the weight remained relative stable under saturated solutions of sodium chloride (RH75%) and magnesium chloride (RH35%). In vivo analgesic activity of the Ibuprofen implants significantly inhibited acetic acid induced writhing in mice as compared to the control. The findings of this study showed that Ibuprofen biodegradable implants of uniform character can be formulated using plasticized polymers and their admixtures via the solvent casting technique. The formulations exhibited a dose dependent release of the active principle with formulations containing varying concentrations of carnauba wax showing a more marked decrease in drug release over time. The implants also recorded a significant degree of analgesia in mice.
