Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design.

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.

Synthesis of phytochemicals-stabilized gold nanoparticles and their biological activities against bacteria and Leishmania.

Nanoscale materials have shown promising results in the field of medicine as therapeutic agents and drugs delivery vehicles. In the current study, gold nanoparticles (AuNPs) were prepared by a green and facile method using the aqueous extract of Rhazya stricta decne as a source of reducing and stabilizing agents. The bio-fabricated AuNPs were characterized by UV-visible spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM) and FTIR spectroscopy. Antimicrobial activities of the biosynthesized AuNPs were tested against Leishmania tropica (HTD7), E. coli and S. aureus. AuNPs were the most effective agents in inhibiting the growth of intra-THP-1 amastigotes at 100 µg/mL concentration (IC50 = 43 µg/mL) after 48-h incubation. In addition, the prepared AuNPs also displayed good activity against E. coli (MIC = 25.0 µg/mL) and Bacillus subtilis (50.0 µg/mL). Interestingly, biogenic AuNPs did not exhibit cytotoxic effect against the THP-1 cells after 24 h exposure. The findings of this study conclude that phytochemicals-stabilized AuNPs could be a safe and effective source of antimicrobial agents.

Pharmaceutical Development of Intraperitoneal Arachis hypogaea as a Renal Protective Agent.

BACKGROUND: Kidneys are among the vital organs of the human body; therefore, damage from any exogenous/endogenous agent may put human life at risk. Arachis hypogaea (AH) contains different free radical scavenging flavonoids, stilbenes, and tannins. This research aimed to elucidate the possible nephroprotective mechanism of AH methanolic crude extract (AHcr) and n-hexane oil fraction (AHO) against gentamycin-induced nephrotoxicity. METHODS: After the extraction of the crude oil of the plant, they were tested against a Gentamycin (GM)-treated group of Swiss Albino mice for their nephroprotective action. Animals were divided into six (6) equal groups with five (5) animals in each group. These groups were: control group (0.5 mL normal saline via intraperitoneal -i.p), gentamycin group (gentamycin 100 mg/kg i.p), Silymarin + gentamycin group (Silymarin 50 mg/kg and gentamycin 100 mg/kg i.p), plant extract (AHcr1) and gentamycin group (AHcr1 250 mg/kg and gentamycin 100 mg/kg i.p), AHcr2 + gentamycin group (AHcr2; 500 mg/kg and gentamycin 100 mg/kg i.p) and the hexane oil fraction (AHO) + gentamycin (AHO 1 mL/kg and GM 100 mg/kg i.p). After completion of doses, animals were sacrificed for the collection of blood to further investigate biochemical changes and histopathological changes in kidney tissues. RESULTS: Serum creatinine, urea, and blood urea nitrogen significantly increased (p < 0.001) in the gentamycin-treated group as compared to the control group. The elevated level of serum creatinine, urea, and blood urea nitrogen was decreased significantly (p < 0.001) in groups treated with AHcr and AHO compared to the gentamycin group. Similarly, the histopathological study of kidney tissues from the gentamycin group showed tubular necrosis, vacuolation, and fibrosis. CONCLUSIONS: The effect of crude extract and hexane soluble fraction of AH caused a significant reversal of gentamycin-induced nephrotoxicity.

Development and Evaluation of Self-Emulsifying Drug-Delivery System-Based Tablets for Simvastatin, a BCS Class II Drug.

Background: Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs. This study aimed at formulating and characterization of SEDDS-based tablets for simvastatin using castor and olive oils as solvents and Tween 60 as surfactant. Methods: The liquids were adsorbed on microcrystalline cellulose, and all developed formulations were compressed using 10.5 mm shallow concave round punches. Results: The resulting tablets were evaluated for different quality-control parameters at pre- and postcompression levels. Simvastatin showed better solubility in a mixture of oils and Tween 60 (10:1). All the developed formulations showed lower self-emulsification time (˂200 seconds) and higher cloud point (˃60°C). They were free of physical defects and had drug content within the acceptable range (98.5%-101%). The crushing strength of all formulations was in the range of 58-96 N, and the results of the friability test were within the range of USP (≤1). Disintegration time was within the official limits (NMT 15 min), and complete drug release was achieved within 30 min. Conclusion: Using commonly available excipients and machinery, SEDDS-based tablets with better dissolution profile and bioavailability can be prepared by direct compression. These S-SEDDSs could be a better alternative to conventional tablets of simvastatin.

Fabrication of a Double Core-Shell Particle-Based Magnetic Nanocomposite for Effective Adsorption-Controlled Release of Drugs.

There has been very limited work on the control loading and release of the drugs aprepitant and sofosbuvir. These drugs need a significant material for the control of their loading and release phenomenon that can supply the drug at its target site. Magnetic nanoparticles have characteristics that enable them to be applied in biomedical fields and, more specifically, as a drug delivery system when they are incorporated with a biocompatible polymer. The coating with magnetic nanoparticles is performed to increase efficiency and reduce side effects. In this regard, attempts are made to search for suitable materials retaining biocompatibility and magnetic behavior. In the present study, silica-coated iron oxide nanoparticles were incorporated with core-shell particles made of poly(2-acrylamido-2-methylpropane sulfonic acid)@butyl methacrylate to produce a magnetic composite material (MCM-PA@B) through the free radical polymerization method. The as-prepared composite materials were characterized through Fourier-transform infrared (FTIR)spectroscopy, scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), energy-dispersive X-Ray Analysis (EDX), and thermogravimetric analysis (TGA), and were further investigated for the loading and release of the drugs aprepitant and sofosbuvir. The maximum loading capacity of 305.76 mg/g for aprepitant and 307 mg/g for sofosbuvir was obtained at pH 4. Various adsorption kinetic models and isotherms were applied on the loading of both drugs. From all of the results obtained, it was found that MCM-PA@B can retain the drug for more than 24 h and release it slowly, due to which it can be applied for the controlled loading and targeted release of the drugs.

Screening of Rhamnus Purpurea (Edgew.) Leaves for Antimicrobial, Antioxidant, and Cytotoxic Potential.

Exploring new antimicrobial and cytotoxic drugs has been one of the most active areas of research. Rhamnus purpurea (Edgew.) buckthorn (Rhamnaceae) is a wild shrub traditionally used in Pakistan for the treatment of various ailments including cancer and infectious diseases. The aim of this study is to find novel antimicrobial and cytotoxic agents of plant origin. The crude methanol extract and full range of fractions of R. purpurea leaves were screened for the said activities using in vitro antimicrobial, antioxidant, and cytotoxic models following standard protocols. The antimicrobial activity was evaluated using the agar well diffusion method, while the antioxidant activity was assessed with 1,1-diphenyl-2-picryl hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The cytotoxic effect was investigated against the human cancer cell lines i.e. Caco-2 (gut), A549 (lung), HepG2 (liver), and MDA-MB-231 (breast) by MTS assay. In addition, toxicity studies were conducted on renal and alveolar primary epithelial cells (HRPTEpiC and HPAEpiC, respectively). Phytochemical investigation showed the presence of secondary metabolites such as alkaloids, saponins, tannins, glycosides, phenols, carbohydrates, proteins, and flavonoids. The n-hexane and chloroform fractions showed significant activity against Staphylococcus aureus (MIC 0.60 and 0.68 mg/mL, respectively), Salmonella typhi (MIC 0.48 and 0.45 mg/mL, respectively), and Bacillus subtilis (MIC 0.54 and 0.76 mg/mL, respectively). Among fungal strains, crude methanol and chloroform fractions exhibited significant activity against Fusarium solani (MIC 0.53 and 0.44 mg/mL, respectively) and Aspergillus niger (MIC 0.47 and 0.42 mg/mL, respectively). The crude methanol, n-hexane and chloroform fractions revealed the highest antioxidant activity at 1000 µg/mL, compared to that of ascorbic acid. The n-hexane fraction showed a significant cytotoxic effect against Caco-2, A549, and HepG2 cell lines with IC50 values of 5.65 ± 0.88, 5.50 ± 0.90, and 4.95 ± 1.0 µg/mL, respectively. Similarly, the chloroform fraction depicted significant activity against Caco-2, A549, and HepG2 cell lines with IC50 values of 4.55 ± 1.25, 4.65 ± 1.55, and 2.85 ± 0.98 µg/mL, respectively. The crude methanol extract and almost all fractions exhibited the highest selectivity index (>2.0) for Caco-2, A549, and HepG2 cancer cell lines, providing safety data for this study. The results showed that R. purpurea leaves have excellent antimicrobial, antioxidant, and cytotoxic potential and warrant further studies to search for novel compounds for the said activities.

Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against Leishmania tropica (HTD7).

Leishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus, the search for new chemical compounds is instantly desirable. In this study, we used two compounds, i.e., 10-hydroxy chondrofoline and tafenoquine, for their antileishmanial activity against L. tropica (HTD7). First, the cytotoxicity assay of the test compounds against THP-1 cells was carried out, and these compounds were found safe. Intra-THP-1 amastigote activity (in vitro) was performed, which was then followed by the in vivo activity of 10-hydroxy chondrofoline in the murine cutaneous leishmaniasis (CL) model. A total of three concentrations were used, i.e., 25, 50, and 100 µM, to check the in vitro activity of the test compounds against the amastigotes. 10-hydroxy chondrofoline was found to be the most potent compound in vitro (and thus was selected for in vivo studies) with an LD50 value of 43.80 µM after 48 h incubation, whilst tafenoquine had an LD50 value of 53.57 µM. In vivo activity was conducted by injecting 10-hydroxy chondrofoline in the left hind foot of the infected BALB/c mice, where it caused a statistically significant 58.3% (F = 14.18; p = 0.002) reduction in lesion size (0.70 ± 0.03 mm) when compared with negative control (1.2 ± 0.3 mm).