Improvement Of Bioavailability Research Articles

Oral delivery of dihydroartemisinin for the treatment of melanoma via bovine milk exosomes.

Cancer, particularly skin cancer, is a major cause of mortality worldwide, with melanoma being one of the most aggressive and challenging to treat types. Current therapeutic options, such as dacarbazine (DTIC), have limitations due to dose-related toxicities like liver toxicity. Therefore, there is a need for new and effective treatments for melanoma. Dihydroartemisinin (DHA), derived from artemisinin compounds known for their anti-malarial properties, has shown promise as an anti-cancer agent. However, the clinical use of DHA faces challenges such as low solubility and toxicity, which limit its therapeutic efficacy. To overcome these challenges, we developed an exosomal formulation of DHA to enhance its anti-cancer activity and reduce metastasis. Exosomes, biological vesicles, contain many biological macromolecules such as DNA, RNAs, and many other proteins, involved in intercellular communication, were isolated and loaded with DHA using the sonication method. The loaded exosomes were characterized for size (90-103nm), polydispersity index (PDI: 0.119-0.123), and zeta potential (-23 to -28mV). In vitro studies demonstrated the efficacy of DHA-loaded exosomes through cytotoxicity and apoptosis assays. The molecular mechanism of action was further elucidated using immunoblotting analysis, focusing on key proteins involved in apoptosis and metastasis regulation, including Bax, Bcl-2, survivin, and MMP-9. Furthermore, we observed a significant improvement in oral bioavailability (2.8-fold) with the exosomal formulation and enhanced in vivo anti-cancer activity of DHA. Notably, treatment with Exo-DHA resulted in strong enhancement of tumor growth suppression and reduced melanoma cell metastasis compared to free DHA.

Effect of polyoxylglycerides-based excipients (Gelucire®) on ketoprofen amorphous solubility and crystallization from the supersaturated state

Polyoxylglycerides-based solid mixtures, commercially known as Gelucire®, are excipients commonly used for bioavailability improvement of poorly water-soluble drugs. However, their effect on solutions containing hydrophobic drugs above crystalline solubility has not yet been explored. The goal of this study was to investigate the impact of a mix of two commercial Gelucire® with high HLB values (Gelucire®50/13 and Gelucire®48/16) on the amorphous solubility and crystallization from supersaturated solutions of ketoprofen, used as model drug. The results evidenced a strong interaction between Gelucire® components and the drug-rich nanodroplets generated upon liquid–liquid phase separation. This led to two important consequences: on one hand, the drug amorphous solubility was decreased, together with the amorphous-to-crystalline solubility ratio; on the other hand, the enlargement and coalescence of the drug-rich droplets were prevented. This stabilizing effect towards the drug-rich phase was comparable to, or even stronger than, that obtained with traditional amorphous polymers (PVP or HPMC) and contributed to inhibiting drug crystallization. Notably, the impact of Gelucire® on drug crystallization from the supersaturated state depended on its micellar behaviour: the monomeric form (below 50 μg/mL) accelerated the formation of crystals, whereas pre-micellar aggregates (50–500 μg/mL) and solubilizing micelles (above 500 μg/mL) inhibited drug crystallization. These findings will contribute to a better understanding of the behaviour of supersaturated drug solutions in the presence of Gelucire® and will facilitate the rational design of supersaturating drug delivery systems containing these excipients.

Sustainable Food Ingredients: Micro-Algae as Source Bioactive Compounds

Microalgae hold immense promise as a sustainable, bioactive source of functional food additives, presenting a unique profile of polyunsaturated fatty acids (PUFAs), carotenoids, vitamins, peptides, and polysaccharides with notable health benefits. Known for their ability to produce compounds like astaxanthin and lutein, Haematococcus pluvialis, Chlorella zofingiensis, and Spirulina contribute to antioxidant, anti-inflammatory, cardiovascular, and visual health when incorporated into food products. Unlike traditional crops, microalgae cultivation requires fewer resources (minimizing land, water, and carbon footprint) while achieving higher photosynthetic efficiency, making them a sustainable solution well-aligned with modern food production goals. However, despite their potential, the mainstream adoption of microalgae-derived bioactives is limited by challenges such as high production costs, complex extraction processes, and stringent regulatory barriers, particularly in markets like the EU. To address these limitations, advancements in photobioreactor technology, biorefinery approaches, and genetic engineering have shown promise in enhancing yield and reducing costs, thereby positioning microalgae as economically viable alternatives to synthetic additives. Furthermore, innovations in encapsulation and bioavailability improvement are advancing, making microalgal compounds more effective and stable in various food systems. This article explores the significant role microalgae could play in food sustainability, reviewing recent research and industry insights to propose practical solutions that encourage broader integration of microalgal bioactives in global markets. Through strategic technological improvements and supportive policy frameworks, the food industry could embrace microalgae-derived compounds, paving the way for resilient food systems that address consumer demands for natural, health-promoting ingredients. With ongoing academic and industrial collaboration, microalgae’s high nutritional value and environmental benefits can be leveraged to support both human health and ecological sustainability, signifying their crucial place in future food innovation.

In-vivo and in-vitro assessment of curcumin loaded bile salt stabilized nanovesicles for oral delivery.

Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability. The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety. The effect of formulation variables (type of span, SDC % to total lipid content Span/Cholesterol molar ratio) on physicochemical characterization and in vitro drug release in simulated intestinal fluid was investigated. Furthermore, in-vivo protective effect of bilosomes on hepatic and renal functions was also studied. and conclusion. The results revealed that the best curcumin loaded bilosomal formulation showed spherical nanovesicular morphology with particle size 145.1 ± 19.42nm with highly reasonable %EE (93%), Zeta potential (≥ -30mv), prominent controlled in-vitro release reaching 55.18 ± 1.10 after 96h. The formulation also showed good storage stability with negligible differences in physical features and content. The IC50 values of bilosomal, niosomal, and free curcumin were 216.50, 211.44, and 121.63mmol/ml, respectively revealing that the unencapsulated curcumin displayed high toxicity on Caco2 cell line (nearly 2 folds). Additionally, the prepared bilosomes showed significant in-vivo hepatic and renal protection in liver cirrhosis induced rats with conservation to all liver and renal markers and histopathological morphology. The study assumes the effectiveness and safety of oral delivery of curcumin loaded bile salts stabilized nanovesicles and its powerful commandment for further investigations.

A Comprehensive Review of the Functional Potential and Sustainable Applications of Aronia melanocarpa in the Food Industry.

Aronia melanocarpa (black chokeberry) is gaining attention in the food and health sectors due to its rich polyphenolic compounds and potent antioxidant properties. This paper provides a comprehensive review of the current research on the functional applications, bioavailability improvement strategies, and potential uses of Aronia melanocarpa in the food industry. The review highlights key developments in processing techniques, such as microencapsulation and nanotechnology, aimed at enhancing the stability and bioavailability of its active compounds. In addition, the paper explores the diversification of Aronia products, including juices, fermented beverages, and functional foods, and the growing market demand. The potential uses of Aronia melanocarpa leaves and by-products for sustainable production are also examined. Finally, the paper addresses the challenges of consumer acceptance, astringency removal, and the need for further research into the metabolic mechanisms and health benefits of Aronia melanocarpa. Future prospects for the Aronia melanocarpa industry, particularly its role in natural and sustainable food markets, are discussed, with an emphasis on innovative product development and the efficient use of by-products.

Enhanced Oral Bioavailability and Biodistribution of Voriconazole through Zein-Pectin-Hyaluronic Acid Nanoparticles.

Nanotechnology-based drug delivery systems offer a solution to the pharmacokinetic limitations of voriconazole (VRC), including saturable metabolism and low oral bioavailability. This study developed zein/pectin/hyaluronic acid nanoparticles (ZPHA-VRC NPs) to improve VRC's pharmacokinetics and biodistribution. The nanoparticles had a spherical morphology with an average diameter of 268 nm, a zeta potential of -48.7 mV, and an encapsulation efficiency of 88%. Stability studies confirmed resistance to pH variations and digestive enzymes in simulated gastric and intestinal fluids. The in vitro release profile showed a controlled release, with 8% of the VRC released in 2 h and 16% over 24 h. Pharmacokinetic studies in rats demonstrated a 2.8-fold increase in the maximum plasma concentration and a 3-fold improvement in bioavailability compared to free VRC. Biodistribution analysis revealed enhanced VRC accumulation in key organs. These results suggest that ZPHA-VRC NPs effectively improve VRC's therapeutic potential for oral administration.

Ketoconazole-Fumaric Acid Pharmaceutical Cocrystal: From Formulation Design for Bioavailability Improvement to Biocompatibility Testing and Antifungal Efficacy Evaluation.

Development of cocrystals through crystal engineering is a viable strategy to formulate poorly water-soluble active pharmaceutical ingredients as stable crystalline solid forms with enhanced bioavailability. This study presents a controlled cocrystallization process by cooling for the 1:1 cocrystal of Ketoconazole, an antifungal class II drug with the Fumaric acid coformer. This was successfully set up following the meta-stable zone width determination in acetone-water 4:6 (V/V) and pure ethanol. Considering the optimal crystallization data, laboratory scale-up processes were carried out at 1 g batch size, efficiently delivering the cocrystal in high yields up to 90% pure and single phase as revealed by powder X-ray diffraction. Biological assays in vitro showed improved viability and oxidative damage of the cocrystal over Ketoconazole on human dermal fibroblasts and hepatocarcinoma cells; in vivo, on Wistar rats, the cocrystal increased oral Ketoconazole bioavailability with transient minor biochemical transaminases increases and without histological liver alterations. Locally on Balb C mice, it induced no epicutaneuous sensitization. A molecular docking study conducted on sterol 14α-demethylase (CYP51) enzyme from the pathogenic yeast Candida albicans revealed that the cocrystal interacts more efficiently with the enzyme compared to Ketoconazole, indicating that the coformer enhances the binding affinity of the active ingredient.

Tailoring cilnidipine nanostructured lipid carriers loaded transdermal patch for the treatment of hypertension: optimization, ex vivo and in vivo studies

The current investigation aimed to develop nanostructured lipid carriers (NLCs) as a potential transdermal drug delivery system for the improvement of cilnidipine (CIL) bioavailability. The high-pressure homogenization (HPH) method was utilized for the formulation of NLCs. Box-Behnken Design (BBD) was utilized to optimize CIL NLCs for entrapment efficiency, particle size and zeta potential. The resultant NLCs had a mean particle size of 98.2 ± 05.08 nm, a zeta potential of −16.1 ± 2.05 mV and an entrapment efficiency of 92.51 ± 4.18%. Transmission electron microscopy (TEM) revealed spherical or elongated particles for CIL-NLCs. The optimized NLCs were embedded in the transdermal patch and were formulated utilizing the solvent casting method and investigated for CIL content, physical characteristics, skin permeation and in vivo pharmacokinetics study. In vivo pharmacokinetics experiments with an NLCs-embedded transdermal patch show, an increase in C max and T max , 1305.66 ± 7.96 ng/mL and 4 h, respectively, when compared to the oral CIL dose. The flux values for ex vivo permeation studies for the CIL NLCs patch were determined to be 82.54 ± 4.80 µg/cm2/h. The bioavailability of CIL-loaded NLCs transdermal patch was found to be 2.9-fold greater than that of oral drug suspension, thus confirming the improvement of bioavailability of CIL by NLCs loaded transdermal patch.

A Comprehensive Review on Imperative Role of Ionic Liquids in Pharmaceutical Sciences.

Ionic liquids (ILs) are poorly-coordinated ionic salts that can exist as a liquid at room temperatures (or <100 °C). ILs are also referred to as "designer solvents" because so many of them have been created to solve particular synthetic issues. ILs are regarded as "green solvents" because they have several distinctive qualities, including better ionic conduction, recyclability, improved solvation ability, low volatility, and thermal stability. These have been at the forefront of the most innovative fields of science and technology during the past few years. ILs may be employed in new drug formulation development and drug design in the field of pharmacy for various functions such as improvement of solubility, targeted drug delivery, stabilizer, permeability enhancer, or improvement of bioavailability in the development of pharmaceutical or vaccine dosage formulations. Ionic liquids have become a key component in various areas such as synthetic and catalytic chemistry, extraction, analytics, biotechnology, etc., due to their superior abilities along with highly modifiable potential. This study concentrates on the usage of ILs in various pharmaceutical applications enlisting their numerous purposes from the delivery of drugs to pharmaceutical synthesis. To better comprehend cuttingedge technologies in IL-based drug delivery systems, highly focused mechanistic studies regarding the synthesis/preparation of ILs and their biocompatibility along with the ecotoxicological and biological effects need to be studied. The use of IL techniques can address key issues regarding pharmaceutical preparations such as lower solubility and bioavailability which plays a key role in the lack of effectiveness of significant commercially available drugs.

Bioavailability improvement by atomic layer coating: Fenofibrate a case study

Biopharmaceutical Classification Systems (BCS) class II drugs show poor solubility and high permeability in the body. Fenofibrate (FF) is a classic example of a BCS class II drug, used to treat high cholesterol and triglyceride (fat-like substances) levels in the blood. Atomic layer coating (ALC) is a surface engineering technology adapted from the semiconductor industry, where metal oxides are coated one atomic layer at a time over the active pharmaceutical ingredients (API) particles. ALC coating was proven to improve the processability, alter the hydrophilicity, improve the stability, and fine-tune the release of drugs. Herein, we report the intervention of ALC coating in enhancing the bioavailability of a poorly water-soluble drug (fenofibrate) in the animal model. The physical properties of uncoated fenofibrate were compared with those of zinc oxide-coated and silicon oxide-coated fenofibrate. Following the application of the coatings, the structural integrity (both chemical stability and solid-state stability) of the active pharmaceutical ingredient (API) remained uncompromised, as corroborated by 1H NMR and powder X-ray diffraction analyses. Notably, zinc oxide-coated fenofibrate exhibited favorable flow characteristics, whereas no discernible enhancement in flow behavior was observed for silicon oxide-coated fenofibrate. The results from contact angle measurements suggest that the silicon oxide-coated fenofibrate exhibits superior wetting behavior, as indicated by a contact angle nearing 0°. The application of ALC demonstrates an enhanced dissolution rate when compared to the uncoated active pharmaceutical ingredient (API) while leaving its equilibrium solubility unaffected. Coating the API with silicon oxide improves particle hydrophilicity and wetting properties, whereas zinc oxide coating aids in particle de-agglomeration, thereby enhancing their interaction with an aqueous medium. In vivo bioavailability studies conducted on rodents and larger animal (dog) models indicate a substantial increase in bioavailability (approximately 2 times) for the silicon oxide-coated API in comparison to the uncoated API, as determined by the area under the curve (AUC). Furthermore, the Cmax values for the silicon oxide-coated API also demonstrate a significant increase (approximately 3 times) over the uncoated API. Notably, an oral subacute toxicity study of ALC silicon-coated fenofibrate revealed no toxic effects attributable to the coating. This study underscores the potential of ALC in augmenting the bioavailability of BCS(II) drugs.

Role of Chronotherapy in the Management of Hypertension: An Overview

: The rise in age-adjusted mortality rates from hypertension and hypertensive diseases over the last several years suggests that hypertension is one of the main risk factors for heart disease. As a result, managing hypertension, both via preventive and therapeutic medicine, involves a heavy socioeconomic burden. This review paper's objective is to summarize information on chronotherapy techniques, which can make it possible for an active component to be distributed predictably and at a pace that may also minimize the patient’s illness symptoms. To incorporate published research and review papers, a comprehensive review of the literature from many sources during the past 25 years was conducted. This paper summarizes the principle and method of the chronotherapy technique. The review also throws light on different approaches that could be used to meet the need for medication for the hypertensive patient according to the circadian cycle. From the study, it was concluded that different formulation approaches are there that can work according to the principle of chronotherapy with improvement in drug bioavailability and patient compliance. To encourage future researchers to include chronotherapy in the creation of additional formulations, this review study intends to shed light on various benefits and methods of chronotherapy.

Development and bioavailability improvement of Resiquimod in the form of solid lipid nanoparticles

The present study aims to develop Resiquimod's Solid Lipid Nanoparticles (SLNs) for topical drug delivery. To evaluate the physicochemical characterization of Resiquimod, lipids, polymers, surfactants &amp; other additives. Formulation &amp; Evaluation of SLNs for particle size analysis, Zeta potential, entrapment efficiency, polydispersity index (PDI), and % yield of produced SLNs. Based on the current studies, it can be said that Resiquimod solid lipid nanoparticles were effectively created and optimized. Hydrogels of prepared SLNs can be applied topically to treat skin conditions such as actinic keratoses (AKs). Different concentrations of lipids and surfactants were used to design SLNs. Mannitol showed much effectiveness as a Cryoprotectant. The drug's excipient Research on the compatibility of drugs, lipids, polymers, and their combinations using FTIR and DSC confirms that the drugs and excipients do not interact chemically. The Nanoparticles in the SLN droplets were intact, non-aggregated, and almost spherical according to scanning electron microscopy (SEM) pictures. The particle size of SLNs loaded with Resiquimod ranges from 208 to 503 nm. This could contribute to the SLNs' more extended blood circulation period. It was discovered that the PDI was less than 0.6. Adequate stability was demonstrated by the negative charge of the zeta potential in the formulation of SLNs. The results are encouraging and represent a novel contribution of Resiquimod SLNs in Topical Drug Delivery.

Enhancement of oral bioavailability of ibrutinib using a liposil nanohybrid delivery system.

Liposils, synthesized via the liposome templating method, offer a promising strategy for enhancing liposome stability by employing a silica coating. This study focuses on the development of nanocarriers utilizing silica-coated nanoliposomes for encapsulating the poorly water-soluble drug, ibrutinib. Ibrutinib-loaded nanoliposomes were meticulously formulated using the reverse-phase evaporation technique, serving as templates for silica coating, resulting in spherical liposils with an average size of approximately 240 nanometers. Comprehensive characterization of the liposil's physical and chemical properties was conducted using various analytical methods, including dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Liposils demonstrated superior performance compared to ibrutinib-loaded nanoliposomes, showing sustained drug release profiles in simulated intestinal fluids and resistance to simulated gastric fluid, as confirmed by dissolution studies. Moreover, ibrutinib liposils exhibited a significant increase in half-life (4.08-fold) and notable improvement in bioavailability (3.12-fold) compared to ibrutinib suspensions, as determined by pharmacokinetic studies in rats. These findings underscore the potential of liposils as nanocarriers for orally delivering poorly water-soluble drugs, offering enhanced stability and controlled release profiles, thereby improving bioavailability prospects and therapeutic efficacy. This approach holds promise for addressing challenges associated with the oral administration of drugs with limited solubility, thereby advancing drug delivery technologies and clinical outcomes in pharmaceutical research and development.

Lipid-based nanodelivery systems of curcumin: Recent advances, approaches, and applications

Despite its many beneficial effects, pharmaceutical applications of curcumin (CUR) are limited due to its chemical instability, low solubility/absorption and weak bioavailability. Recent advances in nanotechnology have enabled the development of CUR-loaded nanodelivery systems to tackle those issues. Within many different nanocarriers developed for CUR up to date, lipid-based nanocarriers (LBNs) are among the most extensively studied systems. LBNs such as nanoemulsions, solid lipid carriers, nanostructured phospholipid/surfactant carriers are shown to be potential delivery systems capable of improving the solubility, bioavailability, and chemical stability of CUR. The particle characteristics, stability, bioavailability, and release properties of CUR-loaded LBNs can be tailored via optimizing the formulation and processing parameters. This paper reviews the most recent studies on the development of various CUR-loaded LBNs. Approaches to the improvement of CUR bioavailability and release characteristics of LBNs are discussed. Furthermore, challenges in the development of CUR-loaded LBNs and their potential applications are presented.

House cricket protein hydrolysates alleviate hypertension, vascular dysfunction, and oxidative stress in nitric oxide-deficient hypertensive rats.

Edible insects with high protein content and bioactive peptides with health promotion against chronic disease. Deficiency of nitric oxide (NO) contributes to hypertension, a leading cause of cardiovascular diseases and death worldwide. This study assessed the antihypertensive effects of house cricket protein hydrolysates (HCPH) in NO-deficient hypertensive rats. Male Sprague-Dawley rats (n = 12/group) were hypertensive after the administration of Nω-nitro-L-arginine methyl ester (L-NAME) at a dose of 50 mg/kg body weight (BW)/day in drinking water for 7 weeks. The animals were then treated with HCPH (250 or 500 mg/kg BW/day) or lisinopril (Lis) (1 mg/kg BW/day) for the last 4 weeks of L-NAME administration. Blood pressure (BP), vascular function, and structural changes, endothelial NO synthase (eNOS), and p47phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression in aortic tissues, plasma nitrate/nitrite, plasma angiotensin-converting enzyme (ACE) activity, and oxidative stress markers in blood and tissues were evaluated. Induction of hypertension resulted in significantly elevated BP, decreased plasma nitrate/nitrite concentration, abolished vascular function, and increased vascular wall thickness. Overproduction of carotid and mesenteric superoxide, increased plasma, heart, and kidney malondialdehyde, and protein carbonyl levels, and increased plasma ACE activity were observed. Down-expression of eNOS with overexpression of p47phox NADPH oxidase subunit was also found in L-NAME hypertensive rats. Oral treatment with HCPH, particularly at a dose of 500 mg/kg BW/day, significantly alleviated these alterations in a manner comparable to that of Lis. HCPH improved vascular function and exerted antihypertensive effects, mainly due to the improvement of NO bioavailability, reduction of oxidative stress, and inhibition of ACE.

A Novel Prodrug Strategy Based on Reversibly Degradable Guanidine Imides for High Oral Bioavailability and Prolonged Pharmacokinetics of Broad-Spectrum Anti-influenza Agents.

We present orally administrable prodrugs (OSC-GCDIs) of guanidino oseltamivir carboxylate (GOC) based on guanidine cyclic diimide (GCDI) to treat influenza viruses. By concealing the guanidine group, which significantly limits the intestinal absorption, its prodrugs OSC-GCDIs demonstrate dramatic improvement of oral bioavailability. The most promising antiviral substance OSC-GCDI(P) readily forms covalent adducts with serum proteins via a degradable linker after the intestinal absorption. Subsequently, the active species, GOC, is released from the conjugate in a sustained manner, which greatly contributes to improving pharmacokinetic properties. Because of the remarkable improvements in both oral bioavailability and longevity of its active metabolite, OSC-GCDI(P) demonstrates outstanding therapeutic efficacy against both wild-type and oseltamivir-resistant (H275Y) influenza virus strains in a mouse infection model, even with a single oral administration.

Improvement of Bioavailability of Sildenafil Citrate Through Taste Masked Orodispersible Film for Pulmonary Hypertension Management.

The oral bioavailability of sildenafil citrate is approximately 43%, primarily limited by the low aqueous solubility and first-pass effect. Considering the drug properties and biopharmaceutical considerations, this study aimed to develop an immediate release, taste masked orodispersible film (ODF) of sildenafil citrate for the efficient management of pulmonary arterial hypertension (PAH). The optimization was done by applying 32 full-factorial design. The drug-loaded film was prepared and evaluated for the physical and mechanical parameters like; thickness, disintegration time, tensile strength, elongation, swelling index, content uniformity, disintegration and in vitro drug release in pH 6.2 stimulated salivary fluid. The FTIR and DSC data proved excellent compatibility between the drug and polymers used. The time taken for disintegration by the optimized film was about 62.66s, while the drug release was observed ~ 96% in 10min. Pharmacokinetic studies exhibited better sildenafil plasma level (p < 0.05) and Cmax (p < 0.001) of orally disintegrating film which is significantly higher than the oral drug solution. The AUC0-8 (24874.425 ± 1234.45ng. h/mL) in the oromucosal application was 1.2-fold more (p < 0.0001) than the control. The presence of sweetening and flavoring agents in the formulation masked the drug bitterness, resulting in a higher intake of the formulation in rats compared to the unmasked drug solution, as observed with in vivo taste masking studies. The importance of ODF as a feasible, effective, and optimal approach for delivering sildenafil citrate via oromucosal administration for the treatment of PAH was successfully highlighted by these results.

Carbon Nano-Dots based potentiometric sensor for the assay of the antiviral agent; Valacyclovir: In-Depth DFT Calculations, application to the pharmaceutical formulation and greenness assessment

Valacyclovir (VAL), as a prodrug to acyclovir antiviral agent, has recently held a lot of interest for its efficacy boosting owing to the significant improvement in bioavailability. This makes it a successful candidate in the management of herpes simplex strains as well as CORONA viruses. In this work a carbon nano dot-modified glassy carbon electrode (GCE) has been optimized as potentiometric sensor for the assay of VAL through a systematic approach. A mixture components of polyvinyl chloride (PVC) membrane have been selected and fine-tuned for optimum sensitivity and selectivity. The best results have been obtained by drop casting a blend in % w/w of PVC; 30.85, tricrasyl phosphate (TCP) as plasticizer; 64.32, phosphotungstic acid (PT) as cation exchanger; 1.61 and phosphorus – nitrogen-doped carbon nano-dots (PNCDs); 3.22 over the GCE. The density function theory (DFT) calculations have been applied to the optimized structures of VAL and the CDs and have proven high binding affinity of 46 kcal/mol dominated by π-π stacking and hydrogen bonding. The developed sensor has exhibited a swift response time of six seconds at a 5.00 pH value. The ICH guidelines have been applied to validate the optimized parameters. A good linearity range has been obtained from 1.18 × 10-3 down to 1.07 × 10-6 M for a correlation coefficient 0.9996 with a Nernstian slope of 33.16 mV/decade. The greenness has been assessed using the AGREE approach, giving a score of 0.8, which has indicated the environmental friendliness. An average % recovery of almost 99.00 % was obtained by application to the tablet formulations and furtherly it has been monitored by the standard addition method, giving recoveries varied from 98.00 and up to 102.00 % for relative standard deviation values (%RSD) less than 1.50 %, evidencing efficiency for application in the quality control laboratories.

Contrasting the pharmacokinetic performance and gut microbiota effects of an amorphous solid dispersion and lipid nanoemulsion for a poorly water-soluble anti-psychotic

Increasing attention is being afforded to understanding the bidirectional relationship that exists between oral drugs and the gut microbiota. Often overlooked, however, is the impact that pharmaceutical excipients exert on the gut microbiota. Subsequently, in this study, we contrasted the pharmacokinetic performance and gut microbiota interactions between two commonly employed formulations for poorly soluble compounds, namely 1) an amorphous solid dispersion (ASD) stabilised by poly(vinyl pyrrolidone) K-30, and 2) a lipid nanoemulsion (LNE) comprised of medium chain glycerides and lecithin. The poorly soluble antipsychotic, lurasidone, was formulated with ASD and LNE due to its rate-limiting dissolution, poor oral bioavailability, and significant food effect. Both the ASD and LNE were shown to facilitate lurasidone supersaturation within in vitro dissolution studies simulating the gastrointestinal environment. This translated into profound improvements in oral pharmacokinetics in rats, with the ASD and LNE exerting comparable ∼ 2.5-fold improvements in lurasidone bioavailability, compared to the pure drug. The oral formulations imparted contrasting effects on the gut microbiota, with the LNE depleting the richness and abundance of the microbial ecosystem, as evidenced through reductions in alpha diversity (Chao1 index) and operational taxonomical units (OTUs). In contrast, the ASD exerted a ‘gut neutral’ effect, whereby a mild enrichment of alpha diversity and OTUs was observed. Importantly, this suggests that ASDs are effective solubility-enhancing formulations that can be used without comprising the integrity of the gut microbiota – an integral consideration in the treatment of mental health disorders, such as schizophrenia, due to the role of the gut microbiota in regulating mood and cognition.

Formulation Optimization and Characterization of Solid Lipid Nanoparticles of Apixaban.

Unpredictable situations such as clotting of blood, deep vein thrombosis, and pulmonary embolism arise in the body, which is the leading cause of mortality. Such conditions generally arise after surgery as well as after treatment with oral anticoagulant agents. Apixaban is a novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Apixaban has a log P of 2.71 with poor solubility and reported maximum bioavailability of approximately 50%. Hence, the current research mainly focused on the improvement of solubility, bioavailability, and therapeutic efficacy of Apixaban via solid lipid nanoparticles (SLN). The SLN was developed using the hot-homogenization method using a high-pressure homogenizer. The drug-lipid compatibility study was assessed by the FTIR, and the thermal analysis was performed using differential scanning calorimetry (DSC). During the scrutiny of lipids, the highest solubility of Apixaban was estimated in the glyceryl monostearate, hence selected for the formulation. Moreover, the colloidal solution was stabilized by the polyethylene glycol 200. The Design of Expert software (Version 13, Stat-Ease) was implemented for the optimization analysis by considering the 3-independent factors and 2-dependent parameters. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1. Box-Behnken design was applied along with ANOVA, which showed a p-value less than 0.05 for the dependent parameters such as particle size and entrapment efficiency (p-value: 0.0476 and 0.0379). The optimized batch F10 showed a particle size of 167.1 nm, -19.5 mV zeta potential, and an entrapment efficiency of 87.32%. The optimized batch F10 was lyophilized and analyzed by Scanning electron microscopy (SEM), which showed a particle size of 130 nm. The solid powder was filled into the capsule for oral delivery. The marked improvement in solubility and bioavailability was achieved with F10- loaded Apixaban via Solid lipid nanoparticles. Moreover, the sustained released profile also minimizes the unseen complications that occur due to the clotting of blood.