Enhancing flowability of lamivudine through quasi-emulsion solvent-diffusion (QESD) crystallization: A comprehensive study on surfactant impact, particle morphology by QbD concepts and tablet compression challenges.

Lamivudine (LMD), an enantiomer of 2'-deoxy-3'-thiacytidine, plays a crucial role in combatting HIV-1 and managing hepatitis B virus infections. Despite its effectiveness, challenges arise from its difficult flowability and tendency to agglomerate during storage, necessitating a granulation step before tablet compression, as direct compression has proven ineffective. This study aimed to optimize Lamivudine spherical agglomerates using response surface methodology, delving into the intricate relationship between design factors (concentration of tween, span, and acetone) and experimental outcomes (yield and particle size) through central composite design. Analysis of variance (ANOVA) was employed for optimization, with the Quasi-emulsion solvent-diffusion (QESD) crystallization technique utilized for the checkpoint batch. This technique, involving a single solvent and antisolvent with surfactants, showcased remarkable enhancements in flowability and reduced storage agglomeration. The impact of various surfactants [Hydroxy Propyl Methyl Cellulose (HPMC), polysorbate 80, and sorbitane monooleate] on particle morphology, flowability, and storage agglomeration during crystallization was thoroughly assessed. While achieving direct compression into tablets, the porous structure of LMD agglomerates presented challenges in tablet press production speeds, prompting adjustments such as reducing punch speed or implementing a precompression step. Positive outcomes were realized for disintegration and in vitro drug release in comparison to direct compression and wet granulation methods. In conclusion, the QESD crystallization technique successfully yielded hollow, spherical LMD agglomerates with enhanced properties, representing a significant milestone in pharmaceutical formulation.

From seeds to survival rates: investigating Linum usitatissimum's potential against ovarian cancer through network pharmacology.

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan-Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics.

Enhancement of Anticorrosive Performance of Cardanol Based Polyurethane Coatings by Incorporating Magnetic Hydroxyapatite Nanoparticles.

The present investigation demonstrates renewable cardanol-based polyol for the formulation of nanocomposite polyurethane (PU) coatings. The functional and structural features of cardanol polyol and nanoparticles were studied using FT-IR and 1H NMR spectroscopic techniques. The magnetic hydroxyapatite nanoparticles (MHAPs) were dispersed 1-5% in PU formulations to develop nanocomposite anticorrosive coatings. An increase in the strength of MHAP increased the anticorrosive performance as examined by immersion and electrochemical methods. The nanocomposite PU coatings showed good coating properties, viz., gloss, pencil hardness, flexibility, cross-cut adhesion, and chemical resistance. Additionally, the coatings were also studied for surface morphology, wetting, and thermal properties by scanning electron microscope (SEM), contact angle, and thermogravimetric analysis (TGA), respectively. The hydrophobic nature of PU coatings increased by the addition of MHAP, and an optimum result (105°) was observed in 3% loading. The developed coatings revealed its hydrophobic nature with excellent anticorrosive performance.

Development, Statistical Optimization and Characterization of Fluvastatin Loaded Solid Lipid Nanoparticles: A 32 Factorial Design Approach.

The purpose of the present research work was to design, optimize, and evaluate fluvastatin-loaded solid lipid nanoparticles (FLV-SLNPs) using 32 factorial design for enhancing the bioavailability. Fluvastatin has several disadvantages, including the low solubility and substantial first-pass metabolism resulting in a low (30%) bioavailability and a short elimination half-life. FLV-SLNPs were prepared using the nano-emulsion technique. For the optimization of the FLV-SLNPs, a total of nine formulations were prepared by varying two independent factors at three levels, using full factorial design. In this design, lipid (A) and surfactant (B) concentrations were chosen as independent factors, whereas entrapment efficiency (Y1) and in-vitro drug release (Y2) were selected as the dependent variables. Additionally, the prepared SLNPs were characterized for X-ray diffraction, Fourier transform-infrared spectroscopy, and differential scanning calorimetry. These studies revealed that there were no interactions between the drug and the selected excipients and the selected formulation components are compatible with the drug. Pharmacokinetic studies in rats confirmed significant improvement in AUC and MRT of SLNPs in comparison with the pure drug indicating the enhanced bioavailability of SLNPs. This study provides a proof-of-concept for the fact that SLNPs can be effectively developed via experimental factorial design, which requires relatively minimal experimentation.

Standardization of topical preparations for finger-tip unit-Awareness and attitudes among pharmacists and dermatologists and suggestions to improve standardization of topical drug dosing-A two-phase cross-sectional survey.

BACKGROUND: Standardization of topical therapy dosage is important to ensure optimum use and dosage of topical medications. One of the concepts frequently used in the standardization of topical treatment is the Finger-tip unit (FTU). While practitioners, both dermatologists and pharmacists, are generally aware of FTU, practical use is less. OBJECTIVES: We aimed to evaluate views and practices related to FTU among both dermatology and pharmacy faculty and to elicit and validate suggestions for improving standardization. METHODS: We surveyed a group of Dermatologists and Pharmacists-in two phases-in phase 1 (n = 44), an electronic survey was used as a tool to understand their practices regarding FTU, and to obtain suggestions regarding standardization of topical medication delivery. In phase 2 (n = 40), the main suggestions for improvement were resent to the group to rate and validate the same. RESULTS: The awareness of FTU was high among the experts, but practical use of the FTU for patient counselling was less frequent. The group gave suggestions to standardize applications. All these suggestions got high ratings on both feasibility and possible effectiveness in the second phase, with the highest rating being for the suggestion of "Placing QR codes on ointment/cream tubes which link to websites with educational materials/ videos on FTU/topical drug dosing." CONCLUSION: Awareness regarding FTU is high among both dermatologists and pharmacists, however practical use is less. Strategies to improve standardization of topical drug dosing can be formulated through collaboration involving both dermatologists and pharmacists.

Design, Synthesis, and In Vitro Evaluation of Novel Indolyl DiHydropyrazole Derivatives as Potential Anticancer Agents.

Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers.

A detailed analysis of synonymous codon usage in human bocavirus.

Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory and gastroenteric infections in children. To date, four distinct subtypes have been identified worldwide. HBoV1 is the most frequently detected bocavirus in clinical samples derived from the respiratory tract. HBoV has a single-stranded DNA genome, which encodes two nonstructural proteins, NS1 and NP1, and two structural proteins, VP1 and VP2. Despite a large number of available HBoV sequences, the molecular evolution of this virus remains enigmatic. Here, we applied bioinformatic methods to measure the codon usage bias in 156 HBoV genomes and analyzed the factors responsible for preferential use of various synonymous codons. The effective number of codons (ENC) indicates a highly conserved, gene-specific codon usage bias in the HBoV genome. The structural genes exhibit a higher degree of codon usage bias than the non-structural genes. Natural selection emerged as dominant factor influencing the codon usage bias in the HBoV genome. Other factors that influence the codon usage include mutational pressure, gene length, protein properties, and the relative abundance of dinucleotides. The results presented in this study provide important insight into the molecular evolution of HBoV and may serve as a primer for HBoV gene expression studies and development of safe and effective vaccines to prevent infection.

Nephro-protective potential of Morus alba, a prospective experimental study on animal models.

CONTEXT: Morus alba L. (Moraceae) is traditionally used for the treatment of urinary incontinency due its strong diuretic properties. OBJECTIVE: The present study explores the renal protective effects of M. alba, due to its free radical scavenging properties, in order to provide experimental evidence for its established use. MATERIALS AND METHODS: Ethanolic extract (200 mg/kg/d) derived from M. alba fruit was employed in rabbits as a co-therapy (GM-al) with gentamicin (80 mg/kg/d) for a period of 3 weeks. Biochemical kidney functioning parameters, urinary isozymes, and histopathological examination were performed. RESULTS: The results showed that ethanol extract of Morus alba L. prevented alterations in serum creatinine (4.02 ± 0.14, p < 0.0001), blood urea nitrogen (54.18 ± 2.60, p < 0.0001), and serum uric acid levels (2.34 ± 0.12, p < 0.001). However, a decrease in creatinine clearance and urinary volume was observed in experimental groups. Histopathological examination and urinary enzymes excretion also suggested the protective role of the extract. DISCUSSION AND CONCLUSIONS: The co-administration of M. alba with gentamicin prevented renal functioning alterations expected with the use of gentamicin alone. Therefore, it can be concluded that M. alba to protect from kidney damage, which may be because of its free radical scavenging and diuretic properties.

Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion.

Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer-Peppas kinetic model with an R (2) of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).

Mentha piperita in nephrotoxicity--a possible intervention to ameliorate renal derangements associated with gentamicin.

OBJECTIVE: Free radical generation has a strong role in the pathogenesis of renal damage associated with the use of gentamicin. Therefore, the present study was carried out to evaluate the renoprotective effect of Mentha piperita against gentamicin induced nephrotoxicity. MATERIALS AND METHODS: A total of 24 male rabbits were divided into 4 groups receiving normal saline, gentamicin, M. piperita extract and co-therapy of extract and gentamicin respectively. Gentamicin was provided as 80 mg/kg/day intramuscularly and extract was given 200 mg/kg/day orally for a period of 21 days. Serum and urinary biochemical parameters and histological changes were studied for each group. The impact of the extract on the antibacterial action of gentamicin was also evaluated. RESULTS: Animals treated with gentamicin showed derangements in serum and urinary biochemical parameters. These alterations were reversed by treatment with M. piperita extract. The histological changes showed in gentamicin group were also reverted by treatment with the extract. Further the plant did not influence the efficacy of gentamicin with respect to its antimicrobial properties. CONCLUSION: Co-therapy of M. piperita with gentamicin successfully attenuated biochemical kidney functioning derangements and morphological changes associated with gentamicin.

Citrullus colocynthis failed to combat against renal derangements, in spite of its strong antioxidant properties.

Gentamicin is a potent antibiotic, effective against Gram negative bacteria. The most common adverse effect of gentamicin is nephrotoxicity. Present study was aimed to explore the protective potentials of Citrullus colocynthis against gentamicin induced nephrotoxicity due to its strong antioxidant properties. Toxic doses of gentamicin (80 mg/kg/day, i.m.) were administered alone and as co-therapy with the extract of C. colocynthis (25 mg/kg/day, p.o.). Physiological, biochemical and histological examinations were performed to compare the experimental and toxic groups (n = 6) with control group animals. Co-therapy of C. colocynthis with gentamicin protected changes in the body weight, blood urea nitrogen, creatinine clearance, proteins and lactate dehydrogenase excretions. However, a significant rise in serum creatinine and serum uric acid with fall in serum calcium and serum potassium was observed, which were significantly different from control group animals. Necrotic and ruptured tubules were also found abundantly. This study revealed that co-theapy of C. colocynthis with gentamicin for twenty one days, failed to protect renal injury associated by gentamicin in spite of its strong antioxidant properties.