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AAPS PharmSciTech Jun 2024Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic...
Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (K) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.
Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Drug Liberation; Excipients; Molecular Weight; Pilot Projects; Povidone; Solubility; Thermodynamics
PubMed: 38862663
DOI: 10.1208/s12249-024-02845-3 -
Journal of Pharmaceutical Analysis May 2024The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and... (Review)
Review
The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
PubMed: 38799236
DOI: 10.1016/j.jpha.2023.12.009 -
Journal of Oleo Science 2024Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to...
Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to one molecule of glycerol. Drug delivery system (DDS) is defined as a formulation to distribute drugs into the human body. The unique properties of MCTs have garnered interest in using them as excipients in DDS. Even though there are many significant effects attributed to the use of MCTs, especially in modulating the rate of drug delivery in various DDS, they are all limited and intermittent. This warrants a detailed summary of the previous studies on the use of MCTs in various DDS. Therefore, this review focuses on presenting a systematic review of previous studies on the use of MCTs in the last six years and explores the types and effects of MCTs on DDS that employ various types of delivery routes. A systematic search through PubMed, Science Direct and Scopus was performed. Keywords like "medium-chain triglycerides", "medium-chain fatty acids", "medium-chain triglycerides and their fractions", "medium-chain fatty acids and their fractions", "MCTs", "MCFA", "in drug delivery", "in drug delivery system" and their combinations were used. The synonyms of the words were also used to extend the search. A total of 17 articles that met the inclusion criteria were identified. Findings from this review have identified the several MCTs and their fractions used in DDS that employed the oral/enteral, topical, transdermal, parenteral, and pulmonary routes of drug delivery. The review also highlights that the usage of MCTs in DDS results in a better transportation of drugs into the human body.
Topics: Humans; Drug Delivery Systems; Carbon; Excipients; Fatty Acids; Triglycerides
PubMed: 38432994
DOI: 10.5650/jos.ess23204 -
Vaccines Nov 2023Aluminium adjuvants are commonly used in vaccines to boost the effects of vaccination. Here, we assessed the benefits and harms of different aluminium adjuvants vs.... (Review)
Review
Concentrations, Number of Doses, and Formulations of Aluminium Adjuvants in Vaccines: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials.
Aluminium adjuvants are commonly used in vaccines to boost the effects of vaccination. Here, we assessed the benefits and harms of different aluminium adjuvants vs. other aluminium adjuvants or vs. the same aluminium adjuvant at other concentrations, administered a different number of doses, or at different particle sizes used in vaccines or vaccine excipients. We conducted a systematic review with meta-analysis and Trial Sequential Analysis to assess the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We obtained data from major medical databases until 20 January 2023 and included 10 randomized clinical trials of healthy volunteers. The comparisons assessed higher vs. lower aluminium adjuvant concentrations; higher vs. lower number of doses of aluminium adjuvant; and aluminium phosphate adjuvant vs. aluminium hydroxide adjuvant. For all three comparisons, meta-analyses showed no evidence of a difference on all-cause mortality, serious adverse events, and adverse events considered non-serious. The certainty of evidence was low to very low. None of the included trials reported on quality of life or proportion of participants who developed the disease being vaccinated against. The benefits and harms of different types of aluminium adjuvants, different aluminium concentrations, different number of doses, or different particle sizes, therefore, remain uncertain.
PubMed: 38140168
DOI: 10.3390/vaccines11121763 -
International Journal of Antimicrobial... Dec 2023The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency,... (Review)
Review
The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency, international guidelines recommend reducing administration of fluoroquinolones, in the context of growing resistance and the long-lasting and potentially disabling side effects of these drugs. The favoured drug to replace fluoroquinolones is fosfomycin trometamol (FT), a well-known derivate of phosphonic acid with broad-spectrum activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant (MDR) strains. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently reduced the susceptibility breakpoint for E. coli from 32 mg/L to 8 mg/L regarding FT used for uUTIs. This might lead to increased appropriate use of oral fosfomycin target therapy against E. coli and other microorganisms, and may be associated with a high likelihood of success. For species such as Klebsiella spp, particularly MDR strains, the absence of clinical breakpoints might lead to reduced use of oral fosfomycin, particularly if minimum inhibitory concentration is not available. To address this issue, this review presents an overview of the preclinical evidence on the activity of FT, and a systematic review of the clinical activity of FT in uUTIs in women, and in the prevention of infectious complications after prostate biopsy. The findings indicate that the safety and microbiological and clinical effectiveness of a single oral dose of FT are similar to that for comparator regimens with longer treatment schedules in women with uUTI, and FT can be considered a viable alternative to fluoroquinolones for antimicrobial prophylaxis in prostate biopsy. These observations and a broad clinical experience support the empirical use of FT for treating uUTI and indicate that FT is a promising candidate to effectively counteract antibiotic-resistant uUTIs throughout Europe.
Topics: Male; Female; Humans; Fosfomycin; Anti-Bacterial Agents; Tromethamine; Escherichia coli; Expert Testimony; Urinary Tract Infections; Anti-Infective Agents; Fluoroquinolones
PubMed: 37748624
DOI: 10.1016/j.ijantimicag.2023.106983 -
Critical Reviews in Food Science and... Nov 2023Essential oil nanoemulsion may have improved antibacterial properties over pure oil and can be used for food preservation. Ultrasonic cavitation is the most common... (Meta-Analysis)
Meta-Analysis
Essential oil nanoemulsion may have improved antibacterial properties over pure oil and can be used for food preservation. Ultrasonic cavitation is the most common mechanism for producing nanoemulsions, and the impact of processing parameters on droplet properties needs to be elucidated. A systematic literature search was performed in four databases (Science Direct, Web of Science, Scopus and PubMed), and 987 articles were found, 16 of which were eligible for the present study. A meta-analysis was performed to qualitatively assess which process parameters (power, sonication time, essential oil, and tween 80 concentration) can influence the final droplet size and polydispersity and how droplet size is associated with antibacterial activity. We observed that power, essential oil, and tween 80 concentrations added during processing are the critical variables for forming smaller droplets. Ratios of up to 3:1 (surfactant:oil) can produce droplets smaller than 180 nm with antibacterial properties superior to pure oil or isolated compounds. The improved properties of nanoemulsions are associated with the size and chemical composition of the droplet since the proportion of the hydrophobic core (EO) and the hydrophilic outer layer (Tween 80) directly influences the antibacterial mechanism of action.
Topics: Oils, Volatile; Polysorbates; Emulsions; Surface-Active Agents; Anti-Bacterial Agents
PubMed: 35900149
DOI: 10.1080/10408398.2022.2103089