Microbiological acceptance criteria, specifications of herbal drugs and herbal drug preparations in various pharmacopoeias: a global scenario.

PURPOSE: A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region. METHOD: In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated. RESULTS: It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination. CONCLUSION: From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Antibiotic Potentiation Through Phytochemical-Based Efflux Pump Inhibitors to Combat Multidrug Resistance Bacteria.

BACKGROUND: Antimicrobial resistance development poses a significant danger to the efficacy of antibiotics, which were once believed to be the most efficient method for treating infections caused by bacteria. Antimicrobial resistance typically involves various mechanisms, such as drug inactivation or modification, drug target modification, drug uptake restriction, and drug efflux, resulting in decreased antibiotic concentrations within the cell. Antimicrobial resistance has been associated with efflux Pumps, known for their capacity to expel different antibiotics from the cell non-specifically. This makes EPs fascinating targets for creating drugs to combat antimicrobial resistance (AMR). The varied structures of secondary metabolites (phytomolecules) found in plants have positioned them as a promising reservoir of efflux pump inhibitors. These inhibitors act as modifiers of bacterial resistance and facilitate the reintroduction of antibiotics that have lost clinical effectiveness. Additionally, they may play a role in preventing the emergence of multidrug resistant strains. OBJECTIVE: The objective of this review article is to discuss the latest studies on plant-based efflux pump inhibitors such as terpenoids, alkaloids, flavonoids, glycosides, and tetralones. It highlighted their potential in enhancing the effectiveness of antibiotics and combating the development of multidrug resistance. strains. RESULTS: Efflux pump inhibitors (EPIs) derived from botanical sources, including compounds like lysergol, chanaoclavine, niazrin, 4-hydroxy-α-tetralone, ursolic acid, phytol, etc., as well as their partially synthesized forms, have shown significant potential as practical therapeutic approaches in addressing antimicrobial resistance caused by efflux pumps. Further, several phyto-molecules and their analogs demonstrated superior potential for reversing drug resistance, surpassing established agents like reserpine, niaziridin, etc. strains. CONCLUSION: This review found that while the phyto-molecules and their derivatives did not possess notable antimicrobial activity, their combination with established antibiotics significantly reduced their minimum inhibitory concentration (MIC). Specific molecules, such as chanaoclavine and niaziridin, exhibited noteworthy potential in reversing the effectiveness of drugs, resulting in a reduction of the MIC of tetracycline by up to 16 times against the tested strain of bacteria. These molecules inhibited the efflux pumps responsible for drug resistance and displayed a stronger affinity for membrane proteins. By employing powerful EPIs, these molecules can selectively target and obstruct drug efflux pumps. This targeted approach can significantly augment the strength and efficacy of older antibiotics against various drug resistant bacteria, given that active drug efflux poses a susceptibility for nearly all antibiotics.

A Novel RP-HPLC Method for Simultaneous Estimation of Vilanterol Trifenatate, Umeclidinium Bromide and Fluticasone Furoate in Inhalation Dry Powder Formulation.

The dry powder inhalation formulation containing vilanterol trifenatate, umeclidinium bromide and fluticasone furoate intended for the therapy of bronchospasm related to chronic obstructive pulmonary disease and bronchial asthma was selected for the development and validation of a novel, selective, accurate, precise, quick and cost-efficient reversed-phase, high-performance liquid chromatography method. Neither an official monograph nor a single method has yet been published for the simultaneous estimation of these three compounds, which makes this method novel. The stationary phase of an ACE-C18-PFP column (250 mm × 4.6 mm, 5 µ) was used with a mobile phase of 25-mM sodium perchlorate buffer (pH 2.5 adjusted with ortho-phosphoric acid) and acetonitrile (40:60% v/v) at a flow rate of 1 mL/min to optimize chromatographic variables. The column temperature was kept at 40°C, and detection was at 224 nm, which was the isosbestic point of these three drugs. Well-resolved good peak symmetry was obtained for all three molecules by isocratic elution in less than 10 min, and the retention times of vilanterol trifenatate, umeclidinium bromide and fluticasone furoate were found to be 3.7, 5.4 and 8.3 min, respectively. The proposed method was validated as per ICH Q2 (R1) guidelines, and the calibration curves were linear in concentration ranges of 5-35 µg/mL for vilanterol trifenatate, 5-80 µg/mL for umeclidinium bromide and 5-150 µg/mL for fluticasone furoate, with mean % recoveries of 99-100%. The limits of detection and quantitation are 0.15 and 0.45 µg/mL for vilanterol trifenatate, 0.58 and 1.77 µg/mL for umeclidinium bromide and 0.32 and 0.96 µg/mL for fluticasone furoate, respectively. Hence, the proposed RP-HPLC technique was successfully used to quantify the inhalation formulation containing all three compounds.

3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.

OBJECTIVES: The aim of this study was to develop 3-acetyl-11-keto-beta-boswellic acid (AKBA)-loaded polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. METHODS: Polymeric nanomicelles of AKBA were developed by a radical polymerization method using N-isopropylacrylamide, vinylpyrrolidone and acrylic acid. The polymeric nanomicelles obtained were characterized by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In-vitro and in-vivo evaluations of AKBA polymeric nanomicelles gel were carried out for enhanced skin permeability and anti-inflammatory and anti-arthritic activity. KEY FINDINGS: TEM and DLS results demonstrated that polymeric nanomicelles were spherical with a mean diameter approximately 45 nm. FTIR data indicated a weak interaction between polymer and AKBA in the encapsulated system. The release of drug in aqueous buffer (pH 7.4) from the polymeric nanomicelles was 23 and 55% after 2 and 8 h, respectively, indicating sustained release. In-vitro skin permeation studies through excised abdominal skin indicated a threefold increase in skin permeability compared with AKBA gel containing the same amount of AKBA as the AKBA polymeric nanomicelles gel. The AKBA polymeric nanomicelle gel showed significantly enhanced anti-inflammatory and anti-arthritic activity compared with the AKBA gel. CONCLUSIONS: This study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity.

Isoflavonoids from Flemingia strobilifera (L) R. Br. roots.

A new isoflavone (1) isolated from the roots of Flemingia strobilifera (L) R. Br. was identified as 5,7,4'-trihydroxy 8,2',5'-tri(3-methylbut-2-enyl)isoflavone along with the known phytoconstituents: 5,7,2',4'-tetrahydroxyisoflavone (2), 5,7,4'-trihydroxyisoflavone (3) and beta-sitosterol (4). Structure assignments were performed on the basis of spectroscopic data including homo- and heteronuclear 1D and 2D NMR (COSY, HMBC and DEPT) and MS studies. The compounds were tested in vitro for antimicrobial activity and antioxidant activity and compounds (1-3) proved to be moderately active.