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Cubosomes, which are modified cubic phase systems, are looking very promising as a method of delivering both hydrophilic and lipophilic drugs. Transdermal delivery of cubosomes is currently gaining more importance over conventional topical delivery of drugs. The proposed study aimed to produce Lidocaine hydrochloride loaded cubosomes. This study was designed to prepare various formulations of Lidocaine nano cubsomal dispersions at different concentrations of lipid and stabilizer using optimization technique. For the purpose of prolonging the duration of the local anaesthetic action, Lidocaine-loaded cubosomes were developed by bottom up method utilizing Glyceryl mono oleate and Poloxamer 407 in various ratios using the "Quality by Design" approach, 32 factorial design employing statistical software. Within the confidence intervals, the 32 statistical design was effective at forecasting the optimized formulation's composition. Surface morphology, particle size, drug content, poly dispersibility index, zeta potential, entrapment efficiency, and in vitro drug release studies were conducted on the prepared formulations. Several mathematical models were used to conduct and assess an in vitro drug release investigation. The maximal entrapment efficiency for the LH8 formulation, which was validated to have optimum cubosomes dispersion, was reported to be 78 % with vesicle size as 150 nm, Zeta potential 21.5 mV and Poly Dispersibility Index as 0.08 along with an in vitro drug release 80.03 % by the end of 24 hours. A stable dispersion with appreciable results of evaluation parameters of cubosomal dispersion was conferred with formulation LH8. Hence from amongst the nine formulations developed, it is concluded that LH8 is selected as the optimized dispersion to be incorporated into a gel formulation. [ABSTRACT FROM AUTHOR]

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Objective Duchene Muscular dystrophy (DMD) is the common X-linked heterogenous progressive muscular dystrophy characterized by mutations in the DMD gene. The frequency of dystrophin gene mutations is varied in different DMD population. A precise diagnosis can help to reduce the severity of DMD since it aids in planning of targeted medical treatment and required therapies. This study was aimed to investigate the mutation type, their rate and distribution of DMD'S in southern India. Materials & Methods An observational study was conducted on 250 genetically confirmed DMD patients from March,2019 to March,2021. The distribution pattern and rate of mutations (deletion, duplication, nonsense mutations, minor mutations) were investigated. Results Mutation spectrum was studied on 250 DMD patients, of which 63% exon deletion pattern were reported. 16% deletions were detected in proximal hot region (exons 3-28). The duplications were found 21% in the proximal hotspot largest region (exon 3-25). 16% of the patients reported single deletion (45 exon), 10.7% reported deletions of exon 44. Point mutations detected in 6%, small mutations were detected in 1.2%, non-sense mutations were detected in 2% of study population respectively. Missense Mutations were detected in 0.8% of study population. Conclusion This study estimates mutation spectrum of exon deletion pattern (63%) was predominantly identified in distal region; duplication was most frequent in proximal region. Point mutations, Nonsense mutations and small mutations have a least accountability. This study adds a real world evidence for developing research therapies in DMD. [ABSTRACT FROM AUTHOR]

The purpose of the study is to perform pre-formulation studies for alpha-mangostin (α-mangostin) and screening of additives (such as solid lipids, emulsifiers and cryoprotectants) and their combinations (ratio of lipids, ratio of drug: lipid, ratio of emulsifier: co-emulsifier and concentration of cryoprotectant) used in the formulation of solid lipid nanoparticles of α-mangostin. This screening is essential for the formulation of solid lipid nanoparticles (SLNP) that provide small particle size and PDI, high entrapment efficiency and zeta potential. This screening offers a rationale for selecting additives and their concentrations for formulating optimized SLNP. Preformulation studies showed melting point of 181.5°C, partition coefficient of 0.359 and drug solubility of 0.3072, 0.4576, 0.4892 and 0.5782 mg/mL in 1.2, 6.8, 7.0 and 7.5 pH buffers respectively. Ultimately, the DSC thermogram defines the sharp endotherm of α-mangostin at 195.98°C. Hot melt homogenization followed by ultrasonication technique is used to develop solid lipid nanoparticles. Process parameters such as homogenization speed (15,000 rpm) and ultra sonication (6 minutes) was optimized based on particle size and PDI. The optimized formulation of SLNP of α-mangostin contain 1:2:0.5:0.5:5 ratio of Drug: Solid lipid (0.8:1.2 ratio of Stearic acid: Precriol ATO5): Poloxamer 407: Sodium taurocholate: Mannitol. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

COVID-19, a respiratory pandemic associated with morbidity and mortality due to the lack of FDA approved drugs for the appropriate preventive or treatment strategies. Repurposed drugs such as antiviral and antimalarials are in clinical trials for the development of novel therapeutic agents for the treatment of SARS-CoV-2 infection. The main protease (Mpro) digests replicase polyprotein to generate non-structural proteins and an endoribonuclease (NendoU), a non-structural protein acts as possible targets because of their prominent role in the replication of SARS-CoV-2. In the current study, the bioflavonoids that passed the Lipinski rule were subjected to in silico molecular docking on SARS-CoV-2 main protease and endoribonuclease using Molegro Virtual Docker v6.0. Molecular dynamic simulation studies (20 ns) were carried out to study protein-ligand complex stability by using Schrodinger, LLC's Maestro Molecular Platform (version 11.8). ADMET properties, target and antiviral potentials were predicted for the top interacting bioflavonoids and significant data were reported. The parameters such as MolDock scores, ReRank scores and interaction poses were predicted for the top interacting phytocompound. In silico analysis showed that hesperetin and malvidin bind effectively at the active site of Mpro and NendoU with a MolDock score of - 100.78 and -86.51 respectively. Molecular dynamic simulations have shown that the protein-ligand complex was stable and exhibits good binding interactions with various amino acids. MM-GBSA studies showed -52.51±5.01 and - 22.80±3.04 free binding energies for hesperetin and malvidin respectively. The current research created a new perspective in understanding hesperetin and malvidin as potent Mpro and NendoU inhibitors, and further research may confirm their therapeutic potentials in COVID-19. [ABSTRACT FROM AUTHOR]

Albuterol sulphate is a Beta-2-adrenergic agonist drug mainly used in the form of nasal inhalations to treat chronic bronchitis and chronic obstructive pulmonary disease (COPD). A simple, rapid, precise chemometricsbased RP-UHPLC method has been developed and validated in its MDI formulations by the QbD approach. The chromatographic separation was achieved by Hibar HR purospher STAR RP-18 encapped column (C18, 250 mm × 4.6 mm, 5 µm) with UV detection ?max 225 nm. The retention time (Rt) for albuterol sulphate was observed as 2.434 over a run time of 5 minutes. Optimization of the method for the quantification of albuterol sulphate in its metered dose inhaler formulations has been performed by using 22 central composite design with response surface methodology that might lessen the solvent consumption, duration, and additional resources. A total of two independent variables, organic phase composition, and flow rate, were analyzed to construct a quadratic process model to examine the effect of independent variables or critical material attributes (CMAs) ahead the observed responses known as the critical method parameters (CMPs) within the designed space. The optimized UHPLC method contains phosphate buffer (10 mM KH2PO4) and acetonitrile (60:40 %v/v) as the mobile phase, which was delivered with a flow rate of 1.0 ml/min and the column was maintained at 40°C. The developed QbD based method was subsequently validated as per ICH Q2 R1 guidelines. The method obeyed linearity within the range of (5-120 µg/mL) with regression R2 of 0.999 for albuterol sulphate. The low coefficients of variation obtained in the intraday and inter-day precision studies indicate précised method. High recovery of albuterol sulphate has been observed within the range of (98.0-102.0 %). The developed method can be intensely employed as a highly robust, accurate, and cost-effective for routine analysis in research labs that competitively separate the drug from its excipients. [ABSTRACT FROM AUTHOR]