Prajesh Prajapati

Development of forced degradation and stability indicating studies of drugs—A review

Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions. It is required to demonstrate specificity of stability indicating methods and also provides an insight into degradation pathways and degradation products of the drug substance and helps in elucidation of the structure of the degradation products. Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. In addition, the regulatory guidance is very general and does not explain about the performance of forced degradation studies. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms and also describes the analytical methods helpful for development of stability indicating method.

Anticounterfeit packaging technologies

Packaging is the coordinated system that encloses and protects the dosage form. Counterfeit drugs are the major cause of morbidity, mortality, and failure of public interest in the healthcare system. High price and well-known brands make the pharma market most vulnerable, which accounts for top priority cardiovascular, obesity, and antihyperlipidemic drugs and drugs like sildenafil. Packaging includes overt and covert technologies like barcodes, holograms, sealing tapes, and radio frequency identification devices to preserve the integrity of the pharmaceutical product. But till date all the available techniques are synthetic and although provide considerable protection against counterfeiting, have certain limitations which can be overcome by the application of natural approaches and utilization of the principles of nanotechnology.

Azeotropic mixture used for development and validation of Lornoxicam in bulk and its tablet dosage form by spectrophotometric method

A novel, safe, economic and sensitive method of spectrophotometric estimation has been developed using Azeoptropic mixture (water:methanol: 60:40, v/v) for the quantitative determination of Lornoxicam, a practically water-insoluble drug. Hence, Lornoxicam stock solution was prepared in Azeoptropic mixture. Lornoxicam showed maximum absorbance at 383 nm. Beers law was obeyed in the concentration range 4–24 μg/mL with regression coefficient of 0.999. The method was validated in terms of linearity (R2=0.999), precision (CV for intra-day and inter-day was 0.28–0.68 and 0.12–0.92, respectively), accuracy (98.03–100.59% w/w) and specificity. This method is simple, precise, accurate, sensitive and reproducible and can be used for the routine quality control testing of the marketed formulations.

Development of a green method for separation and identification of the degradation impurity of isoniazid by SFC-MS/MS

To produce an eco-friendly stability indicating method, the reaction solutions containing degradation products of isoniazid were used for separation and optimized by varying the supercritical fluid chromatography (SFC) conditions. A mixture of supercritical carbon dioxide (SC-CO2) (85%) and modifier dichloromethane:methanol:ethyl acetate:formic acid (70:30:0.5:0.1 v/v/v/v) (15%) was used as a mobile phase and separation was achieved using a C-18 column. The degradation products separated at relative retention times (RRT) of 1.58 and 1.82, respectively. The method was validated as per international standards in terms of selectivity, linearity, precision and recovery. The drug shows a linear response at concentrations between 1 and 100 μg ml−1. The mean values (±%RSD) of the slope, intercept and correlation coefficient were 179009 (±0.3%), 151382 (±0.6%), and 0.9985 (±0.04), respectively. The mean %RSD values for intra- and inter-day precision were 0.63 and 1.29, respectively. The recovery of the drug ranged between 98.82 and 100.68%, when it was spiked into a mixture of solutions in which sufficient degradation was observed. The study was extended to SFC-MS/MS and FT-IR which were carried out to identify the degradation products. The FT-IR spectra and m/z values of the peaks at RRT 1.58 and RRT 1.82 matched with isonicotinic acid and isonicotinamide, respectively.

Analysis and impurity identification in pharmaceuticals

Abstract Impurity is not a much-liked word by pharmaceutical and industry people, because they are concerned about quality. Here we discuss various impurities that might be present in API formulations. To fulfill our purpose we have compiled a variety of regulatory authorities’ guidelines (i.e., ICH, WHO, and pharmacopoeias), which serve in endlessly regulating the impurities by various means. As the impurity present in a drug can affect its quality and thus its efficiency, it is therefore crucial to know about impurities. The current article reveals the different terms, regulatory control, and basic techniques (e.g., HPLC, LC-MS, TLC) that will help novices to understand, identify, and quantitatively estimate impurities and that have the advantage of profiling. This article primarily focuses on identification and control of various impurities (i.e., organic, inorganic, and genotoxic). For any of the substances, quality is the prime objective. Because impurities can alter quality, understanding the various impurities will help in producing quality products.

SFC-MS for the identification and estimation of ethambutol in its dosage form and in human urine samples

An ecofriendly, specific, accurate and precise SFC-MS method (using TurboIonSpray probes) is described for the determination of ethambutol in its pharmaceutical dosage form as well as in human urine samples by using supercritical carbon dioxide (SC-CO2, 90%) as the mobile phase at a flow rate of 2 mL min−1 and methanol : formic acid (100 : 0.1 v/v, 10%) as a modifier at a flow rate of 0.2 mL min−1. Supercritical carbon dioxide (SC-CO2) is an environmentally friendly mobile phase which has outstanding penetration power, negligible toxicity and low viscosity. EMB was determined in less than 5 min using a C18 reverse-phase fused-core column (Inertsil ODS-C18, 100 mm × 4.6 mm, 5 μm). The method was validated according to the International Conference on Harmonization (ICH) and US-FDA guidelines with values of selectivity, specificity, linearity, extraction recovery, matrix effect, accuracy and precision in the working range of 0.1 to 20 μg mL−1 with an accuracy (% RE) of EMB of −6.00 to 6.00%. The proposed method was successfully applied to human urine samples and marketed formulations from various manufacturers.

Densitometric Measurement for Estimation of Ciclesonide in Bulk and Its Dosage Form (Rotacap) by High-Performance Thin-Layer Chromatography

A sensitive method based on high-performance thin-layer chromatography (HPTLC) by using principle of densitometry with UV detection at 7nmax 242 nm for quantitative estimation of major pharmaceutically active compound, ciclesonide, 2-[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9,13-dimethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-8-yl]-2-oxoethyl-2-methylpropanoate, which persists as a newer antiasthmatic drug of glucocorticoid class, is described here. Chromatographic separation was performed by semiautomatic CAMAG HPTLC instrument. The method was validated according to the International Conference on Harmonization (ICH) guidelines, illustrating to be accurate (98.92–100.26%) and precise (CV = 0.43–0.67 for intra-day and CV = 0.58–1.45 for inter-day) within the corresponding linear range. Limit of detection (LOD) and limit of quantification (LOQ) of sample were found to be 100 ng/spot and 303 ng/spot, respectively.