Drug molecule contains various reactive functional groups which are susceptible to react with another reactive functional groups which might be excipients, excipient or drugs impurities formed during manufacturing or storage. The objective of the current review article is to provide a comprehensive review of excipients-drug compatibility study, their degradation product characterization with different analytical methods and further impact of methodologies in pharmaceutical industry for potential stability assessment. The incompatibility of drug excipient was very common due to the reactive functional groups in drugs and excipients. These leads to formation of drug related impurities as well as excipient impurities reaction with active Pharmaceutical Ingredients. Sometimes these impurities found to be mutagenic and genotaxic to human beings. Identification of drug degradation in presence of excipient impurities requires extensive knowledge and adequate analytical characterization data. Systematic literature review and understanding about the drug-excipient chemistry in formulation process is important criteria to select compatible excipient and formulate ideal formulation. The analytical characterization data gives idea about degradation pathway. This paper discusses drug-excipient interactions, compatibility and characterization by different analytical methods with case studies and provides an overview of different excipients compatibility in formulation.
Genotoxins are agents/carriers such as chemical or radiation that can cause the damage to DNA or chromosomal structure, thereby causing mutations and the process are called as genotoxicity. Identification and understanding of genotoxins at a primary stage of drug development would enable us to prevent the potential damage that can be caused by these genotoxic agents. Various regulatory agencies such as International Council for Harmonization and EMEA, USFDA, European Pharmacopeia guidance, guidance for oncology products provide guidelines to limits the level of impurities in drug substances and drug products. Nowadays, conventional protocol of isolation, various spectral analysis high-performance liquid chromatography (LC), Fourier transform infrared to on-line analysis using modern, sophisticated hyphenated tools, like gas chromatography-mass spectroscopy, LC-MS so on, as well as modern software based in silico drug designs are extensively used by industry, research, and development areas and also there is tremendous increase in publications in the literature involving their use. Our review article focused on the various regulatory guidelines, application of hyphenated tools, and in silico techniques in genotoxic impurity and degradation product profiling of small molecules. A brief explanation is made on possible pitfalls in the experimentation and data interpretation. From this review, it concluded that there are various countries having their own regulatory agencies and regulatory guidelines for drug approvals, which may be followed by applying new chemical entities the new drug application title (NDA) in new drug application as well as there are various conventional to modern software based techniques to quantification of genotoxic impurities.
Nature is a treasure hunt of novel molecules which are extensively used by humans for their medicinal values for millennia. Herbal medicines have emerged as life savers all over the world due to their multifunctional and diverse array of activities on the human body. Plants supply numerous bioactive molecules which are capable of treating disease conditions. Plants produce varieties of phytochemicals which are commonly recognized as primary and secondary metabolites. Secondary metabolites are inimitable resources for exploitation for pharmaceuticals, food additives e.t.c. They are often involved in the control of abiotic or biotic stress. They play distinctive roles in the defense mechanism of plants, act as insect repellant, regulate signaling pathways, and also exhibit varied range of pharmacological actions such as antibacterial, antioxidant, anticancer anti-diabetic and others. Secondary metabolites are derived from one or mixed pathways that give rise to formation of various compounds i.e., alkaloids, volatile oils, tannins, glycosides and resins etc. which have great importance in modern medicine. Isopentenyl diphosphate and Shikimic acid pathway serve as primary precursors for the synthesis some of types of secondary metabolites. The present review deals with the brief introduction, significance of secondary metabolites in the plants, biosynthetic pathways, and therapeutic importance of some commonly known secondary metabolites.
A simple, specific and validated reverse phase high performance liquid chromatography method was developed for determination of drug related substances (impurity) of Darunavir in formulation. Method development includes optimization of stationary phase (column) and mobile phase flow rate for the resolution of six known impurities and one unknown impurity and Darunavir. Development of HPLC method for estimation of Darunavir related substance in formulation was carried out on Zorbax SB-C8, 250 x 4.6mm, 5µm by using a gradient mode of the mobile phase flow rate at 1ml/min with the same mobile phase as, ACN : Buffer pH 4.0 (Mobile phase B:Mobile Phase A). The stability-indicating capability of the method was proved through the solution state stability, solid state study and it was concluded that purity threshold was found to be greater than purity angle. A good linear relation exists over the range of 50 to 150 % specification level with a correlation coefficient value of 0.9998Validation of the method was successfully established by performing various validation parameters such as specificity, precision, linearity, accuracy, LOD, LOQ, robustness, ruggedness according to ICH guidelines.zones. ICH guidelines also guide qualification, identification,
Aim: The aim of the research work has to development and validation of dissolution test method for Tapentadol using HPLC method, investigate the effects of stress on dissolution stability by thermal and non-thermal methods. The present research work mainly focused on the evaluation and compares the influence of accelerated-aging conditions on the drug content and in vitro dissolution stability. Place and duration of Study: Department of Pharmaceutical Chemistry, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur (MS). Methodology and Results: Saturated solubility study of tapentadol were carried out using different dissolution media and different conditions such as type of dissolution medium, volume of dissolution medium and rotation speed of paddle were evaluated. Basis of it, dissolution testing were carried out on a suitably calibrated USP Apparatus II (TDT-06L) at 50 ± 1 rpm, under sink conditions in 900 mL of deaerated distilled water at 37±0.5ºC for each test and selected most optimized dissolution parameter which given maximum % release of drug. The drug release was evaluated by high-performance liquid chromatographic method. Also proposed method were validated as per ICH guidelines with respect to system suitability, linearity, precision, accuracy, range, robustness, ruggedness and solution stability parameters were evaluated and the obtained results were within the acceptable range. The stress on dissolution stability of standard powdered drug, tablet formulation and packed strip formulation were investigated by using thermal and non thermal methods. The results obtained in all stress conditions such as thermal, humidity, UV light and visible light were evaluated for drug content and drug release. The results were statistically evaluated by applying two-way ANOVA followed by post-hoc Bonferroni test and their results represented as a graphical plot. Conclusion: In our investigation of stress dissolution of drug it was found that Tapentadol HCl std. drug was susceptible to degradation. The tablet and packaged formulation were susceptible to photolytic degradation indicated by difference in drug content while the release was more affected under UV exposed to tablet and strip packaged formulation as compared to other stress conditions.
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