Tendon plays an important role in regulating body locomotion and providing additional stability to the body. However, tendon is susceptible to injuries and the healing process could be devastating along with the several issues, namely adhesion formations, slow healing and failure at fixation sites, which have deferred the success of proper tendon healing via tendon tissue engineering. This dissertation thus aims to create a sustained dual-drug therapy to address these issues. For adhesion formation, naproxen sodium (NPS) has been shown to be able to avoid this symptom through inhibiting inflammation process.

The motivation for the present study is systematically presented and the aims and objectives of the study are clearly defined. A comprehensive review on modified release drug delivery has been presented to provide the basis for the meltable aqueous dispersion technique as an approach to the formulation of a multiple-unit oral modified release drug delivery system. In addition, a brief discussion on the theory of dissolution testing and the mechanisms and interpretation of the dissolution process has been presented. Naproxen sodium, a potent non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic activity employed in the study, has been briefly discussed. In the present study, the coacervation phase separation technique utilizing ethylcellulose was initially investigated but proved unsuccessful in producing a formulation displaying suitable drug release characteristics. Subsequently, the meltable aqueous dispersion technique utilizing cetostearyl alcohol was successfully employed to formulate a multipleunit modified release naproxen sodium preparation containing 550 mg of naproxen sodium. The use of cetosteary!alcohol, as·a·retarding material, generated modified ·drug release characteristics as a function of its content. Magnesium stearate (anti-tackiness agent) and Span 20 and Tween 60· (surfactants) were incorporated in the formulation to optimize particle size and sphericity. The influence. of various formulation variables on drug release characteristics were investigated: An optimized formulation displaying a desirable modified release profile of naproxen sodium was achieved employing a 1:1 ratio of naproxen sodium:cetostearyl alcohol, 2% m/m .. .. magnesium stearate, and 1%m/m Span 20 dispersed in a liquid manufacturing vehicle of pH 0.6 containing 2% m/m Tween 60. In vitro dissolution studies on the selected formulation showed drug release to be predictable and reproducible, dependent on the dissolution method, agitation rate, and the pH of the dissolution media (i.e. pH-dependent drug release). The density of the microspheres was shown to decrease as the concentration of cetostearyl alcohol increased whilst the mean specific surface area increased with increasing concentrations of cetostearyl alcohol. Differential scanning calorimetric studies reveals a change in the thermograms which is suggestive of eutectic formation. Scanning electron microscopy proved useful in evaluating the integrity and surface morphology of the microspheres as well as in elucidating the drug release characteristics of the formulation. Energy dispersive x-ray microprobe analysis revealed the elemental composition of the microspheres to be a composite of the pure ingredients. X-ray mapping and the line scan depicted the homogenous distribution of drug within the microspheres and confirmed that the formulation is a matrix-type modified release I' preparation. Stability studies were performed on the selected formulation at room temperature (21 :t 1°C), 40°C, 37°C with 80% relative humidity, and at low temperature (5 :t 1°C). The shelf-life of the selected formulation was determined to be 1.29 years. Applying the data to five different kinetic models to investigate the drug release mechanisms showed that first order and cube-root release characteristics were exhibited by the microspheres. / Thesis (M.Sc.)--University of Durban-Westville, 1997.

The research addressed in this thesis focuses on monitoring and characterization of pharmaceutical compounds by laser backscattering. In particular, this study covers two topics: (1) the determination of naproxen sodium solubility in water, and its phase transition; and (2) comparisons of batch and laminar flow tubular crystallizers for the production of paracetamol (acetaminophen) and D-mannitol. Using a Lasentec™ Focused Beam Reflectance Measurement (FBRM) device, the solubility of naproxen sodium in aqueous solutions was determined over a temperature range from 15.2 to 39.7 ℃ With the determination of the solubilities of two pseudopolymorphs, anhydrous and dihydrated naproxen sodium, the phase transition point between these two forms of the pharmaceutical compound was determined to occur at 30.3 ℃ Enthalpy of solution and metastable zone widths were also determined for the experimental conditions. Crystallizations of paracetamol and D-mannitol were performed in a batch crystallizer and in a laminar flow tubular crystallizer (LFTC) system. In the latter system, supersaturation was generated rapidly in the solution being transported through a temperature-controlled tube and recovered in a batch vessel where product crystals were grown to equilibration. Because of the rapid rate at which supersaturation was generated in the LFTC, the resulting crystals were of smaller mean size than those obtained from batch crystallizations. The total time required for crystallization was significantly less with the LFTC than with the batch unit. Additionally, the rapid cooling in the LFTC led to the formation of two different polymorphs of paracetamol, Forms I and II.