708 ds dissolution apparatus cary 60 uv vis

Dissolution tests were performed on all successfully produced formulations via USP apparatus 2 (708-DS Dissolution Apparatus & Cary 60 UV-Vis, Agilent Technologies, USA), using the same parameters and amount of API as in previous studies (1,2). Capsules of a specified formulation containing 25 mg of naproxen underwent dissolution. The set condition in the dissolution test includes 900 ml dissolution medium, temperature of 37.3 ± 0.5 °C and paddle agitation of 50 rpm. The pH of the dissolution medium used was either pH 1.2 or pH 7.4 (the dissolution medium was made according to USP pharmacopoeia), which simulate the gastrointestinal fluid with the absence of enzymes. Spectrophotometric analysis was set to absorbance wavelength at 271 nm. The absorbance readings were taken at 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110 and 120 min.
Difference factor (f₁) and similarity factor (f₂) were used to compare dissolution profiles for various formulations [19 ]. FDA has also recommended using f1 and f2 for comparison of two dissolution profiles [20 (link)–22 ]. In brief, the two dissolution profiles are considered similar if f₁ value is less than 15 or f₂ value above 50 [23 (link)].

All dissolution tests were carried out using USP paddle method (708-DS Dissolution Apparatus & Cary 60 UV-Vis, Agilent Technologies, USA). The formulations in the form of liqui-pellets in capsules were under constant conditions of 900 ml of dissolution medium, paddle agitation of 50 rpm, and temperature of 37.3 ± 0.5°C. Dissolution medium was either HCl buffer solution of pH 1.2 or phosphate buffer solution of pH 7.4 to simulate gastric fluid and intestinal fluid respectively without enzymes. Absorbance (at 271 nm) was taken at time intervals of 5 min until 1 h then time intervals of 10 min for another hour.
All formulations contained 25 mg of naproxen. The reason for choosing 25 mg of naproxen was because of naproxen poor solubility profile at pH 1.2 due to its weak acidic properties. Naproxen would need to be able to dissolve completely at pH 1.2 in order for the dissolution test to be reliable. According to studies by Mora and Martinez (39 ), naproxen solubility at 35°C and pH 1.2 was 1.16 × 10⁻⁴ mol/L or 27 mg/L, hence 25 mg used in test seemed reasonable. As for pH 7.4, naproxen was extremely soluble with a solubility of 1.455 × 10⁻² mol/L or ~3347 mg/L. It should be noted that pH 1.2 sink condition was not maintained and this pH was only used for comparison of various formulations.