Controlled release alginate-chitosan microspheres of tolmetin sodium prepared by internal gelation technique and characterized by response surface modeling

Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.

The patellar tilt angle: correlation of MRI evaluation with anterior knee pain.

The purpose of this study was to analyze the degree of patella tilt and its correlation with the symptoms of anterior knee pain. We used magnetic resonance imaging (MRI) to measure the angle of patella tilt. The patients (n = 128) were classified into two groups. Group 1 (n = 78) included patients who had never had symptoms of anterior knee pain but had MRI for evaluation of the menisci and the ligaments. Group 2 (n = 50) included patients who had MRI for evaluation of anterior knee pain syndrome. Patients who had gross deformities like patellar dislocation, tricompartmental osteoarthritis, or inflammatory arthritis were excluded. The average patella tilt angle was 6.3 (SD = 3.9) and 12.8 (SD = 8.4) degrees, respectively, for the two groups of patients. Twenty-three patients in group 2 underwent arthroscopy because of failure of conservative treatment, and the average patella tilt angle in this subgroup was 16.4 degrees. Our study suggests that patella tilt angle is correlated with the symptoms of anterior knee pain, and indicated that the cause of pain came from the tight lateral retinaculum. In addition, MRI was found to be an accurate and reproducible method of measurement of the patellar tilt angle.