Charmy Kothari

Indigenous plant medicines for health care: treatment of Diabetes mellitus and hyperlipidemia

Medicinal plants have played an important role in treating and preventing a variety of diseases throughout the world. Metabolic syndrome had become a global epidemic, defined as a cluster of three of five criteria: insulin resistance and glucose intolerance, abdominal obesity, hypertension, low high-density cholesterol, and hypertriglyceridemia. The current review focuses on Indian medicinal plant drugs and plants used in the treatment of diabetes and hyperlipidemia. Though there are various approaches to reduce the ill-effects of diabetes and hyperlipidemia and its secondary complications, plant-based drugs are preferred due to lesser side effects and low cost. The current review focuses on twenty-three medicinal plants used in the treatment of Diabetes mellitus and nine medicinal plants used in the treatment of hyperlipidemia. The wealth of knowledge on medicinal plants points to a great potential for research and the discovery of new drugs to fight diseases, including diabetes and hyperlipidemia.

Concurrent Estimation of Amlodipine Besylate, Hydrochlorothiazide and Valsartan by RP-HPLC, HPTLC and UV–Spectrophotometry

Accurate, sensitive and reproducible reversed-phase high-performance liquid chromatography (RP-HPLC), high-performance thin-layer chromatography (HPTLC) and ultraviolet (UV) spectrophopometric methods were developed for the concurrent estimation of amlodipine besylate (AMLO), hydrochlorothiazide (HCTZ) and valsartan (VALS) in bulk and combined tablet dosage forms. For the RP-HPLC method, separation was achieved on a C18 column using potassium dihydrogen orthophosphate buffer (50 mM, pH 3.7) with 0.2% triethylamine as the modifier and acetonitrile in the ratio of 56:44 (v/v) as the mobile phase. Quantification was achieved using a photodiode array detector at 232 nm over a concentration range of 2-25 µg/mL for AMLO, 5-45 µg/mL for HCTZ and 20-150 µg/mL for VALS. For the HPTLC method, the drugs were separated by using ethyl acetate-methanol-toluene-ammonia (7.5:3:2:0.8, v/v/v/v) as the mobile phase. Quantification was achieved using UV detection at 242 nm over a concentration range of 100-600 ng/spot for AMLO, 150-900 ng/spot for HCTZ and 1,200-3,200 ng/spot for VALS. The UV-spectrophotometric simultaneous equation method was based on the measurement of absorbance at three wavelengths; i.e., at 237.6 nm (λmax of AMLO), 270.2 nm (λmax of HCTZ) and 249.2 nm (λmax of VALS) in methanol. Quantification was achieved over the concentration range of 2-20 µg/mL for AMLO, 5-25 µg/mL HCTZ and 10-50 µg/mL for VALS. All methods were validated according to International Conference on Harmonization guidelines and successfully applied to marketed pharmaceutical formulations. Additionally, the three methods were compared statistically by an analysis of variance test, which revealed no significant difference between the proposed methods with respect to accuracy and precision.

Review on Implementation of Multivariate Approach for Forced Degradation Study and Impurity Profiling with Regulatory Considerations

Understanding of shelf-life, expiry periods, degradation kinetics, stability indications, and impurity profiling is of major concern. The present review focuses on the quality-by-design (QbD) approach for optimizing forced degradation conditions for impurity profiling. Analytical issues occurring at the last stage of long-term stability studies are related to unpredicted impurities, which can disturb monitoring of characterized impurities and raise many regulatory issues. The QbD multivariate approach was evaluated within the framework of the liquid chromatography (LC) method. The initial investigation is concerned with critical process parameters which can impact on critical quality attributes. Selection of primary and secondary parameters to define a design space with the help of a polynomial equation and Derringer’s desirability value is considered next. Sorting impurities using the multivariate design-of-experiments (DoE) approach can also be beneficial to reduce time and cost, whilst providing a robust process. Much emphasis is given to application of Q8 and Q9 International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines to improve quality, safety, and efficacy studies.Graphical abstract

Development and validation of a high-performance thin-layer chromatographic—densitometric method for the quantification of guggulsterones E and Z in a polyherbal formulation containing Commiphora Mukul

The present article focuses on the quantitative analysis of a polyherbal formulation containing arjuna, guggul, and pushkarmoola in a combined dosage form which is used for its cardioprotective, anti-anginal, and hypolipidemic activities. Quantification of guggulsterones E and Z was done by developing and validating a high-performance thin-layer chromatography method after extraction by methanol. Densitometric evaluation was carried out on precoated silica gel G60 F254 high-performance thin-layer chromatography (HPTLC) plates using toluene—ethyl acetate (8:2, v/v) as the mobile phase. Based on the HPTLC results, the methanol extract of guggulsterone was chosen as it showed a better separation of spots as compared to another extract. After postderivatization of plates with anisaldehyde—sulfuric acid (10%) reagent, the methanol extracts gave different color spots (the arjuna extract gave a blue spot, the guggul extract gave orange and brown spot, and pushkarmoola gave dark blue spot). Scanning and densitometric evaluations were done at 251 nm. The calibration curve was plotted in the concentration range of 0.2–1.2 μg spot−1 for both guggulsterone E and guggulsterone Z, and the method was found linear with r2 = 0.9902 and 0.9883, respectively. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines for accuracy, precision, range, linearity, limit of detection (LOD), and limit of quantification (LOQ). Assay quantitation was performed based on the regression equation obtained from the linearity of the standard guggulsterones E and Z. The developed HPTLC method is fast, simple, precise, specific, and accurate; hence, it can be successfully employed for the quantification of guggulsterones E and Z in polyherbal formulations. Furthermore, the developed method can also be used for the standardization of herbal formulations containing guggulsterones E and Z.

Impurity Profile of Bronchodilators used in Asthma: A Critical Review

BACKGROUND Asthma is defined as a heterogeneous disease usually characterized by chronic airway inflammation (GINA 2016) affecting almost 334 million people worldwide (Global asthma report 2014). Treatment of asthma with a long-acting bronchodilator is important because it reduces the symptoms that occur at night or in the early morning and it is very effective to use as a long term control medication for asthma by preventing asthmatic symptoms. The main objective of this review is to describe the impurity profile and force degradation studies for three major classes of bronchodilators namely β2-adrenoceptor agonists, muscarinic receptor antagonists and xanthine. Unidentified and potential toxic impurities are hazardous to health, so in order to increase the safety of drug therapy; impurities should be identified and determined by selective analytical methods. METHODS Different conditions for degradations like hydrolytic (acidic, basic and neutral), oxidative, photolytic and thermolytic have been discussed in detail for bronchodilators. Furthermore, it is discussed with the name along with number of impurities and degradants present in different matrices including its clinical implication. The name as well as structures of all the observed impurities in different bronchodilators is included, which can aid in impurity profiling. Various analytical methods, including Chromatographic techniques like TLC; HPTLC; HPLC; GC, Spectroscopic techniques like UV; IR; NMR; MS and hyphenated techniques like GC-MS; LC-MS; CE-MS; SFC-MS; LC-NMR; CENMR; LC-FTIR has been used for the identification and quantification of impurities. A general scheme has been presented for the impurity profiling. RESULT Nineteen articles, six patents and fifteen drugs are included in this review. In that, majority (7) of papers are based on HPLC-UV, 5 papers are based on LC-MS, 2 papers are based on LC-MS-NMR, 1 paper is based on LC-NMR, 1 paper is based on GC-MSNMR, 1 paper is based on GC-UV and 1 paper is based on TLC-UV technique for isolation and characterization of impurities. In salbutamol, 7 degradants were found by LC-MS as compare to 4 degradants by HPLC-UV. In bambuterol, 12 degradants were found by LC-MS-NMR as compare to 4 degradants by LC-MS. CONCLUSION After a thorough literature search, LC-MS and LC-MS-NMR techniques are found most useful for impurity profiling. In future, LC-DAD-NMR-MS, CE-ESI-FTICR- MS can also be explored for the isolation and characterization of impurities.

Development and validation of a high-performance thin-layer chromatographic—densitometric method for the quantification of apigenin in Ocimum basilicum L. seed (Takhmaria)

A simple, selective, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method has been developed for the quantification of Ocimum basilicum seeds for their apegenin content. Densitometric evaluation was carried out on precoated silica gel G60 F254 HPTLC plates using toluene—acetone—formic acid (5:4:1, v/v) as the mobile phase. Scanning and densitometric evaluations were done at 340 nm. The calibration curve was plotted in the concentration range of 100–600 ng band−1, and the method was found linear with r2 = 0.995. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines for accuracy, precision, range, linearity, limit of detection (LOD), and limit of quantification (LOQ). The validated HPTLC method was used for the estimation of apigenin in O. basilicum seeds. The developed method can be applicable for the identification and quantification of apigenin in complex mixtures of phytochemical and marker-based standardization of plant samples as well as extracts containing O. basilicum seeds.

Regulatory Need: Harmonized PIC/S GMP, Its Overview and Comparison with WHO GMP

Currently, it is necessary to increase harmonizationefforts in setting regulatory requirements, inspecting and evaluating GMP compliance, licensing manufacturing sites, recalling defective batches and increasing the exchange of information due to the increased globalization regulatory authorities. PIC/S offers attractive and stable platform to respond such challenges of the globalization. PIC/S actively encourage networking by organizing a “PIC/S GMP Forum” which allow non-member authorities, professional and other organizations to meet informally with the PIC/S Committee. PIC/s has established harmonized guide on GMP requirements for inspectorate and industry. There is the complementarity co-operation between the PIC/S and other organization. PIC/S participating authority co-operates actively and avoids the duplication of his member’s efforts. Till date, 46 countries are the member of the PIC/S and 10 countries are under Accession and Pre-Accession Procedure. PIC/S provide the sharing of the inspection report between the member authorities which allow them to prove their GMP facility equivalent to PIC/S standard and resulting into the reduction of the number of inspection and duplication of the inspection. Joining to PIC/S will endorse the Indian pharmaceutical companies to be reliable exporters of quality medicines globally. While for Indian Pharma Companies to meet the PIC/S requirement would not be like cakewalk especially for MSME Pharma segment that needs to upgrade their GMP facilities. Thus it will be challenging for stake holders to join PIC/S but simultaneously there will be bigger hurdles of not joining the PIC/S. While approaching to PIC/S, a careful examination is needed by India during export as maintaining high quality standards for export markets. PIC/S is bringing a great revolution in the GMP standards to establish the high quality in the drug product and thus INDIA should become the member of PIC/S to raise its GMP standards as it is recognized as ‘power house’ of pharmaceutical manufacturing.