Challenges and mitigation strategies associated with Burkholderia cepacia complex contamination in pharmaceutical manufacturing.

Burkholderia cepacia complex (BCC) is a Gram-negative, non-spore-forming bacterium with more than 20 opportunistic pathogenic species, most commonly found in soil and water. Due to their rapid mutation rates, these organisms are adaptable and possess high genomic plasticity. BCC can cause life-threatening infections in immunocompromised individuals, such as those with cystic fibrosis, chronic granulomatous disease, and neonates. BCC contamination is a significant concern in pharmaceutical manufacturing, frequently causing non-sterile product recalls. BCC has been found in purified water, cosmetics, household items, and even ultrasound gel used in veterinary practices. Pharmaceuticals, personal care products, and cleaning solutions have been implicated in numerous outbreaks worldwide, highlighting the risks associated with intrinsic manufacturing site contamination. Regulatory compliance, product safety, and human health protection depend on testing for BCC in pharmaceutical manufacturing. Identification challenges exist, with BCC often misidentified as other bacteria like non-lactose fermenting Escherichia coli or Pseudomonas spp., particularly in developing countries where reporting BCC in pharmaceuticals remains limited. This review comprehensively aims to address the organisms causing BCC contamination, genetic diversity, identification challenges, regulatory requirements, and mitigation strategies. Recommendations are proposed to aid pharmaceutical chemists in managing BCC-associated risks and implementing prevention strategies within manufacturing processes.

Unveiling global public interest and seasonal patterns of antibiotics and antibiotic resistance: An infodemiology study with implications for public health awareness and intervention strategies.

INTRODUCTION: The health-related information-seeking through internet sources has drastically increased throughout the world. This study aimed to analyze the Global public interest on "antibiotics" and "antibiotic resistance". METHODS: The worldwide internet trend for the search terms "antibiotics" and "antibiotic resistance" from February 2017 to February 2022 was obtained using Google trends. The seasonal variation of interest was analyzed using the Seasonal Decomposition of Time Series by Loess. RESULTS: The mean interest for the search term "antibiotics" and "antibiotic resistance" is found to be 78.02 ± 7.5 and 2.3 ± 0.8, which will increase at 2.56 % and 16 % per year. It was observed that there was a significant relationship between antibiotic consumption, the number of physicians, and individuals using the internet in the countries with the search term "antibiotics". The study also indicates that there is a peak in search volume for the term during the COVID-19 Pandemic. CONCLUSION: Our study observed, that antibiotics related search questions on google by the public indicate the chances of antibiotic misuse. The study data suggest the need to raise public awareness about antibiotic use and antibiotic resistance, as well as there is need for intensive monitoring of dispensing and procurement patterns of antibiotics in developing countries.

Formulation Development of Tamoxifen Loaded Lipid Nanoparticle by Taguchi (L12 (211)) Orthogonal Array Design.

BACKGROUND: A better understanding of the biopharmaceutical and physicochemical properties of drugs and the pharmaco-technical factors would be of great help for developing pharmaceutical products. But, it is extremely difficult to study the effect of each variable and interaction among them through the conventional approach. METHODS: To screen the most influential factors affecting the particle size (PS) of lipid nanoparticle (LNPs) (solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC)) for poorly watersoluble BCS class-II drug like tamoxifen (TMX) to improve its oral bioavailability and to reduce its toxicity to tolerable limits using Taguchi (L12 (211)) orthogonal array design by applying computer optimization technique. RESULTS: The size of all LNPs formulations prepared as per the experimental design varied between 172 nm and 3880 µm, polydispersity index between 0.033 and 1.00, encapsulation efficiency between 70.8% and 75.7%, and drug loading between 5.84% and 9.68%. The study showed spherical and non-spherical as well as aggregated and non-aggregated LNPs. Besides, it showed no interaction and amorphous form of the drug in LNPs formulation. The Blank NLCs exhibited no cytotoxicity on MCF-7 cells as compared to TMX solution, SLNs (F5) and NLCs (F12) suggest that the cause of cell death is primarily from the effect of TMX present in NLCs. CONCLUSIONS: The screening study clearly showed the importance of different individual factors significant effect for the LNPs formulation development and its overall performance in an in-vitro study with minimum experimentation thus saving considerable time, efforts, and resources for further in-depth study.

Development of tamoxifen-loaded surface-modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation.

The present study aimed to develop a surface-modified biocompatible nanostructured lipid carrier (NLCs) system using polyoxyethylene (40) stearate (POE-40-S) to improve the oral bioavailability of poorly water-soluble Biopharmaceutics Classification System class-II drug like tamoxifen (TMX). Also aimed to screen the most influential factors affecting the particle size (PS) using Taguchi (L12 (211)) orthogonal array design (TgL12OA). Then, to optimize the TMX loaded POE-40-S (P) surface-modified NLCs (TMX-loaded-PEG-40-S coated NLC (PNLCs) or PNLCs) by central composite design (CCD) using a four-factor, five-level model. The most influential factors affecting the PS was screened and optimized. The in-vitro study showed that increased drug-loading (DL) and encapsulation efficiency (EE), decreased PS and charge, sustained drug release for the prolonged period of the time with good stability and suppressed protein adsorption. The Ex-vivo study showed that decreased mucous binding with five-fold enhanced permeability of PNLC formulation after surface modification with POE-40-S. The in-vitro cytotoxicity study showed that the blank carrier is biocompatible and cytotoxicity of the formulation was dependent on the concentration of the drug. Finally, it can be concluded that the surface-modified PNLCs formulation was an effective, biocompatible, stable formulation in the enhancement of dissolution rate, solubility, stability with reduced mucus adhesion and increased permeability thereby which indicates its enhanced oral bioavailability.