Parenteral suspensions of poorly water-soluble salts for intramuscular administration retain therapeutic drug concentration over a long duration. In vitro drug dissolution testing is a prerequisite to assess batch-to-batch variability as well as to assure appropriate drug release during formulation development. The purpose of the present work was to compare the drug release kinetics of two salts of pramipexole in powdered and suspension forms. The two salts employed for the dissolution study were commercially available soluble salt-pramipexole dihydrochloride monohydrate (PRP HCl) and in-house synthesized poorly water-soluble salt, pramipexole pamoic acid salt (PRP PAM). Modified USP apparatus 2 (paddle) using dialysis sac and open loop USP apparatus 4 (flow-through cell) were used for the in vitro dissolution studies. The drug release was estimated using high-performance liquid chromatography. The release kinetics were statistically analyzed using various mathematical models. Results obtained from in vitro dissolution testing showed an immediate-release profile for PRP HCl and a sustained-release profile for PRP PAM, indicating its long-acting potential. The developed method could discriminate between different particle sizes of the PRP PAM salt. The results indicated that the release profile of the PRP PAM salt using modified USP apparatus 2 with dialysis sac more closely mimicked the desired in vivo conditions of intramuscular administration as compared to open loop USP apparatus 4. The developed dissolution method can be used as a quality control tool for PRP PAM injectable suspension.
Sacubitril/Valsartan (SAC/VAL) is a combination drug used for the treatment of heart failure. In the present work, novel and rapid, sensitive, specific, and robust ultra high-performance liquid chromatography method was developed and validated for the simultaneous estimation of SAC/VAL in presence of their seven related impurities and degradation products. The chromatographic separation was achieved on Accucore XL C8, (100 × 4.6) mm; 3 μm reverse phase column maintained at 30°C. The peaks were eluted using tetrahydrofuran (THF) and 0.1% perchloric acid in water (8:92, %v/v) as a mobile phase A and THF:water:acetonitrile (5:15:80, %v/v/v) as mobile phase B in a gradient mode. The flow rate was set at 0.6 ml/minute and the analytes were monitored in the range of 200-400 nm using a Photo Diode Array (PDA) detector for 21 minutes run time. The method was validated as per ICH Q2 (R1) guideline and all the validation parameters were found within the acceptance criteria. The forced degradation study for SAC/VAL showed that the drugs were prone to acidic, alkaline, and neutral hydrolytic as well as oxidative stress conditions. All the degradation products were separated from each other, SAC/VAL and their impurities showing the stability indicating power of the method. The newly developed method can be used for estimation of assay and related substances from bulk or their finished products with good efficiency.
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