| dc.description.abstract | Diclofenac sodium is a non-steroidal, anti-inflammatory drug used for the relief of pain and inflammation. Many patients have difficulty swallowing tablets and consequently do not take medication as prescribed. To achieve optimum benefit of a drug, it is desirable to present it in a formulation which can rapidly disperse in water. This formulation is easier to swallow, therefore enhancing patient compliance. The aim of this study was to develop a stable diclofenac sodium dispersible tablet for easier oral administration. The first step in the product development was an investigative study into the physico-chemical properties, indications, side-effects and contra-indications of diclofenac sodium. Diclofenac sodium - excipient compatibility studies were performed as part of a preformulation study. Methods of evaluation included differential scanning calorimetry (DSC) and high performance liquid chromatography (HPLC). Four dispersible tablet formulations were developed. Kollidon CL-M (crospovidone) and Disolcel (croscarmellose sodium) were used as disintegrants in concentrations of 2% and 5% of the tablet mass. Tabletting was performed using a Cadmach® (India) single-punch tabletting machine. The four formulations were put on accelerated stability according to ICH guidelines for three months at 25°C/60%RH, 30°C/65%RH and 40°C/75%RH. HPLC was used to determine the identification, chromatographic purity and concentration of diclofenac sodium. Other tests included uniformity of mass, hardness, friability, disintegration, fineness of dispersion, loss on drying and dissolution. Thermal compatibility studies revealed potential interactions between diclofenac sodium and the excipients. Since DSC results only serve as a rough indication of possible interactions, accelerated stability testing using HPLC was used as a more selective method to identify potential interactions between diclofenac sodium and excipients. The HPLC results revealed that no interactions exist between diclofenac sodium and the chosen excipients.
At the end of the stability period, no change in the physical appearance of the tablets was observed, except for the samples stored at 40°C/75% RH which showed a colour change from white to a very light brown after 3 months. Uniformity of mass remained within specification and average tablet mass and diameter remained relatively constant during stability testing. There was an increase in average thickness, hardness, disintegration time and percentage loss on drying with time and increased stress conditions. This correlates with the decrease in friability observed with time. Differences in the disintegration times were noted between Kollidon CL-M® and Disolcel® formulations. The only formulation that disintegrated within 3 minutes was formulation B. Very few particles of formulation B were retained on the 710 urn sieve, indicating a homogeneous dispersion. Assay results for all four formulations were within specification throughout stability and no extra peaks ascribed to diclofenac related compound A or any other impurity were observed. After 30 minutes, more than 85% of diclofenac sodium in formulations A, B and D was dissolved. The diclofenac sodium in formulation C did not dissolve well. This correlates with the slow disintegration times of formulation C's tablets. Dissolution rates of formulations C and D decreased with time and increased stress conditions, with the effect more pronounced in the case of formulation C. It can be concluded from the stability results that 5% Disolcel® as disintegrant was superior to a 2% concentration and to Kollidon CL-M® in concentrations of 2% and 5% of the tablet mass. Formulation B (5% Disolcel®) was chosen as the most favourable formulation with the best marketing possibilities. Stability results were also used to determine storage conditions and set specifications for batch release and stability to ensure that all batches tested against these specifications, meet the requirements for quality, safety and efficacy. | |
