Stability

Artesunate (1) (ART), also called as dihydroartemisinin-12-α-succinate, it is a semisynthetic peroxide-bridged sesquiterpene lactone compound derived from Artemisinin, the bioactive component of the Chinese medicinal herb called Artemisia annua.  An accurate, simple and precise HPLC method was developed and validated for forced degradation studies of drug Artesunate .The column was used C18 column (150X4.6mmX5µm ) column  by isocratic elution. The mobile phase composition consisted of Acetonitrile Water and trifluoroacetic acid (TFA) in the ratio of 55:45:0.1 v/v. The analysis was performed at a 1ml/min flow rate. The analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD) and lower limit of quantification (LOQ) were determined according to International Conference for Harmonization ICH Q2 (R1) guidelines.

In the pharmaceutical industry an impurity is considered, defined the any other organic material besides the drug substance or pharmaceutical ingredients.  The impurity may be formed during the formulation or upon aging of two APIs in medicines. Stability testing is an integral part of pharmaceutical development. The primary purpose of stability testing is to provide supporting evidence on stability behavior of pharmaceutical drug products. Stability is the capacity of a drug product to remain within specifications established to ensure its identity, strength, quality and purity.

Bioanalytical methods of Reverse Phase-High performance liquid chromatography (HPLC) was developed and validated for simultaneous estimation of Isoniazid (INH) and Ciprofloxacin Hydrochloride (CIP HCl) encapsulated in lipid polymeric hybrid nanoparticles (LPNs) in plasma and in organ homogenates of lung, liver, spleen and kidney of mice. Chromatographic separation was done using Agilent® C18 bonded silica column of dimensions 150 × 4.6 mm, 5μmwith flow rate 1.0 ml/min, injection volume 20 µland column temperature 40°C. The mobile phase consists of a mixture of 70 volumes of 0.1 percent v/v of trifluoroacetic acid(TFA) and 30 volumes of acetonitrile (ACN). The results indicated that the developed method was linear and selective for all matrices studied. Analysis of accuracy and precision showed adequate values, with relative standard deviation values lower than 5, which are in accordance with USFDA guidelines for bioanalytical method validation. Isoniazid (INH) and Ciprofloxacin Hydrochloride (CIP HCl) were stable in plasma and tissue homogenates under different storage and processing conditions. This method was applied to study the pharmacokinetic and biodistribution profile of both drugs in free form and in bound state with lipid nanoparticles. The results showed that polymeric nanoparticles showed higher drug accumulation in the target site i.e. lung as compared to non-target organs fulfilling our aim of developing a HPLC method for the simultaneous estimation of both drugs and their application in determination of pharmacokinetic and pharmacodynamic potential of the lipid nanoparticles.

Hard candies are experiencing a renewed popularity as a means of delivering many different drug products. They are used for patients who cannot swallow solid oral dosage forms as well as for medications designed to be released slowly to yield a constant level of drug in the oral cavity or to bathe the throat tissues in a solution of the drug. Knowledge on the formulation parameters as well as the process of cooking parameters such as concentration of corn syrup as well as type of corn syrup, temperature of cooking, moisture content type of cooking vessel helpful in solving the problems, Elegance is out most important parameter for candies as this parameter helps in improving patient compliance. So elegance of the candy can be increased by optimizing the formulation as well as process parameters which in turn helpful in enhancing the stability of the dosage form.

Ibuprofen self-emulsified drug delivery system (IBSEDDS) has been prepared, characterized and optimized to release 100% drug in one hour. The optimal formulation was subjected to stability and bioavailability studies in human volunteers. The stability was conducted under different storage temperature (4oC, room temperature and 37oC) for 8 months and evaluated for in-vitro drug release, particle size and turbidity. Bioavailability was evaluated after administration of a single oral dose of two formulations, test (HPMC capsule containing IBSEDD) and reference (HPMC capsule containing 50 mg drug in soybean oil), by 6 health human volunteers. The results showed that IBSEDDS was stable under different storage temperatures and the drug was more stable at 4oC. The changes in particle size and turbidity were lesser at room temperature.  The pharmacokinetic parameters for test/reference were: the Cmax , 0.892/0.468 ug/ml,  the Tmax, 1/1.5hr and the AUC0-∞, 3.956/1.986 mg.hr/ml. The % RBof IBSEDDS was 199.114. In a conclusion, the IBSEDD formulation stored at 4oC were more stable regarding drug content but samples stored at room temperature were more stable regarding particle size and turbidity. The IBSEDD formulation showed higher rate and extent of drug absorption and higher bioavailability compared to the oily drug solution.

  In the present work the approach of forced degradation study was successfully applied for the development of stability-indicating assay method for determination of Thiocolchicoside in the presence of its degradation products.  The RP-HPLC separation was carried out on Shimadzu® -HPLC 1100 series using a Phenomenex ODS 5µ C18 column (250×4.6mm) with mobile phase comprising of Acetonitrile: Phosphate Buffer (70:30) pH 3.5 v/v at flow rate of 1.0mL/min and UV detection at 260.0 nm. In stress testing a drug substance or the drug product is exposed to an environment vigorous than the normal i.e. at high temperature, high humidity over the period of time called accelerated stability conditions. The drug was subjected to Solid state analysis which includes Humidity studies (40°C/75% RH), photochemical studies (UV light and sunlight exposure) and Thermal studies to apply stress conditions. The method was validated as per ICH guidelines for accuracy, precision, linearity and range, ruggedness and robustness. The linearity of the proposed method was investigated in the range of 80-120% of label claim; the correlation coefficient for Thiocolchicoside was found to be 0.999. The proposed method was found to be simple, specific, linear and rugged and can be used for routine quality control.