Drug Development and Industrial Pharmacy最新文献

Objective: The development of Mirtazapine (MRT)-loaded aquasomes by co-precipitation sonication technique to boost the antidepressant potential of MRT.

Methodology: MRT-loaded aquasomes formulations were prepared using Box-Behnken design to investigate the effect of independent factors including sonication time (X1), sonication temperature (X2), and sugar concentration (X3) on the dependent variables as particle size and drug loading efficiency. The formulation of the optimized formula was verified by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Powder Diffraction (XRPD). Furthermore, the morphology of the formula was evaluated by Transmission Electron Microscopy (TEM). The optimum MRT- loaded aquasomes was assessed for physiochemical properties, in vitro MRT release and in vivo antidepressant effects in mice model.

Results: The results revealed that the optimized formula showed a small particle size of 202.7 ± 3.7 nm and a high loading efficiency of 77.65 ± 2.6%. Thermal DSC and XRPD studies demonstrated the amorphous nature of MRT-loaded aquasomes. The in vitro study demonstrated sustained release of F (opt) 88.16% after 8 h, compared with plain MRT release of 63.06% after 1 h. Mice treated with MRT-loaded aquasomes demonstrated reduced immobility time in behavioral analysis to 37% with MRT-loaded aquasomes, while plain MRT reduced it to 55%.

Conclusion: These results confirmed that the antidepressant effect of MRT was significantly boosted in formulated aquasomes, and thereby they provide a promising carrier nano vesicular system for effective delivery of MRT.

Objective: The present research deals with sequential optimization strategy based on Central Composite Design to optimize the process variables for efficient production of Clitoria teratea (CLT) synthesized silver nanoparticles (AgNPs) using biological synthesis.

Methods: Two substantial factors influencing the dependent variables viz UV-visible absorbance, particle size, zeta potential and polydispersity index (PDI) were identified as NaOH concentration, RH concentration, temperature as independent variables. In-vitro and ex-vivo studies of prepared CLT-AgNPs gel and marketed gel were carried out using dialysis membrane and egg membrane, respectively. In addition, antimicrobial study was also performed on the bacterial strains.

Results: The particles size (114 nm), PDI (0.45), and zeta potential (-29.5 mV) of optimized formulation were found, respectively. In-vitro profile of AgNPs from prepared CLT-AgNPs gel was noted (95.6%) in 8 h. It was found that the prepared CLT-AgNPs gel stimulates fibroblast and agranulocytosis development resulting better and timely wound healing.

Conclusions: The prepared CLT-AgNPs gel can be as a potential substitute in the management and treatment of acute and chronic wounds.

Objective: To investigate the in-situ physicochemical interaction of Rifampicin and Ritonavir - Lopinavir Solid dispersion administered for the treatment of comorbid conditions i.e. Tuberculosis and HIV/AIDS.

Methods: pH-shift dissolution of Rifampicin (RIF) in presence of Ritonavir-Lopinavir solid dispersion (RL-SD) was carried out in USP phosphate buffer 6.8 and FaSSIF. Equilibrium and amorphous solubility were determined for the drugs. Pure drugs, their physical mixtures, and pH-shifted co-precipitated samples were characterized using DSC, PXRD, and FTIR. Fluorescence spectroscopy was used to investigate drug-rich and drug-lean phases. In-vitro and ex-vivo flux studies were also carried out.

Results: The results showed significant differences in the solubility and dissolution profiles of RTV and LOP in the presence of RIF, while RIF profile remained unchanged. Amorphicity, intermolecular interaction and aggregate formation in pH-shifted samples were revealed in DSC, XRD and FTIR analysis. Fluorescence spectroscopy confirmed the formation of drug-rich phase upon pH-shift. In-vitro and ex-vivo flux studies revealed significant reduction in the flux of all the drugs when studied in presence of second drug.

Conclusion: RIF, RTV and LOP in presence of each other on pH-shift, results in co-precipitation in the amorphous form (miscible) which leads to reduction in the highest attainable degree of supersaturation. This reduction corresponds to the mole fraction of the RIF, RTV and LOP within the studied system. These findings suggest that the concomitant administration of these drugs may lead to physicochemical interactions and possible ineffective therapy.

Objective: The present study aimed to assess the radioprotective effect of nanoniosomes loaded by Mentha Pulegium essential oil (MPEO-N nanoparticles) as a natural antioxidant on human peripheral blood mononuclear cells (PBMCs).

Significance: Despite the applications and advantages of ionizing radiation, there are many radiation risks to biological systems that are necessary to be reduced as much as possible.

Methods: MPEO-N nanoparticles were prepared by the lipid thin film hydration method, and its physicochemical characteristics were analyzed. PBMCs were then irradiated with X-ray using a 6 MV linear accelerator at two radiation doses in the presence of nontoxic concentrations of MPEO-N nanoparticles (IC10). After 48 and 72 h of incubation, the radioprotective effect was investigated by measuring survival, apoptosis, and necrosis of PBMCs, using MTT assay and flow cytometry analysis.

Key findings: The hydrodynamic diameter and zeta potential of nanoniosomes were 106.0 ± 4.69 nm and -15.2 ± 0.9 mV, respectively. The mean survival percentage of PBMCs showed a significant increase only at a radiation dose of 200 cGy compared with the control group. The percentages of apoptosis and necrosis of cells in the presence of MPEO-N nanoparticles at both radiation doses and incubation periods (48 and 72 h) demonstrated a significant reduction compared with the control.

Conclusion: MPEO-N nanoparticles as a natural antioxidant, exhibited a favorable radioprotective effect by a significant reduction in the percentage of apoptosis and necrosis of irradiated PBMCs.

Context: Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities.

Objective: This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices.

Methods: ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation.

Results: The ASDs' drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%.

Conclusion: The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%.

Objective: Apigenin and gallic acid are natural compounds that are useful as antioxidant, anti-inflammatory and anticancer agents, especially when used together in combination. Therefore, the development and validation of a simultaneous method of analysis for both compounds in pure form and when encapsulated in an advanced delivery system such as liposomes would be useful.

Methods: Analysis was performed using C18 column under isocratic conditions. The mobile phase was acetonitrile: water containing 0.2% orthophosphoric acid at a ratio of 67:33, flow rate 1 ml/min, and detection wavelength 334 nm for apigenin and 271 nm for gallic acid.

Results: The assay method was linear at the concentration range (5-600 µg/mL) with R² of 1 for both drugs. The method was also shown to be precise and robust with RSD less than 2% with LOD (0.12, 0.1 µg/mL) and LOQ (4.14, 3.58 µg/mL) for apigenin and gallic acid respectively. The method was also applicable for the determination of the entrapment efficiency of both drugs when co-loaded in a nanoliposomal formulation.

Conclusion: The described HPLC method was shown to be suitable, sensitive, and reproducible for the simultaneous identification and quantification of apigenin and gallic acid. The analytical results were accurate and precise, with good recovery, low limit of detection, and the chromatographic assay was accomplished in less than 3 min, suggesting the suitability of the method for routine analysis of both drugs in pharmaceutical formulations.

Objective: To develop Plectranthus amboinicus extract loaded Polyurethane foam dressing for burn wound healing.

Significance: Plectranthus amboinicus is traditionally used as an anti-inflammatory and wound-healing agent. Its incorporation in a PU foam dressing will offer the dual benefits of foam dressing as well as the healing potential of P. amboinicus.

Methods: PU foam dressings were prepared and loaded with P. ambionicus leaf extract (PAE). The dressings were prepared with varying concentrations (0.5-2%) of extract along with Toluene diisocyanate, polypropylene glycol (PPG), and liquid paraffin. The dressings were characterized by Scanning Electron Microscopy and evaluated for Moisture Vapor Transmission Rate, absorption rate, porosity, and mechanical strength followed by in vivo burn wound-healing studies in comparison to a marketed dressing.

Results: The MVTR was found to be optimum in formulations FD2-FD4 with values ranging from 2068.06 ± 0.99 to 2095.00 ± 0.25 g/m²/day. Absorption rate was found to be between 1.27 ± 0.01, 1.31 ± 0.00, and 1.30 ± 0.02 g/cm² for formulations FD2-FD4. Formulations FD1, FD2, FD3, FD4 showed better porosity when compared to other formulations. Formulation FD4 was further characterized by micro-CT and a porosity of 46.32% was obtained. Tensile strength measurement indicated that the selected formulations were flexible enough to withstand regular handling during dressing changes. Acute dermal irritation performed on rabbits showed no irritation, erythema, eschar, and edema. In vivo wound-healing studies performed on albino wistar rats showed that the FD4 formulation has better wound healing property.

Conclusion: Plectranthus ambionicus-loaded PU foam dressing demonstrated promising burn wound-healing potential.

Objective: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions.

Significance, methods, and results: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints.

Conclusion: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.