RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Processing cow ghee (clarified butterfat) with therapeutic herbs, i.e. ghrita, is recognized for augmenting the therapeutic efficacy of plant materials. Ashwagandha ghrita (AG) is an effective Ayurvedic formulation consisting of Indian ginseng, i.e., Withania somnifera (L.) Dunal, the main constituent used to treat infertility, weakness, gynaecological disorders, and general debility. OBJECTIVES: The present investigation was undertaken to corroborate the ethnopharmacological claim of AG as 'Vajikarana Rasayana' for its aphrodisiac potential using bioinformatics (in-silico) and experimental (in-vitro and in-vivo) approaches. METHODS: AG was formulated as per the methods reported in Ayurved sarsangraha. AG was further subjected to HPLC, GCMS analysis, and biological (acute toxicity and aphrodisiac) assessment per the standard procedures. Thirty-eight bioactives of Indian ginseng were subjected to computational studies (molecular docking and network pharmacology) to confirm the plausible mechanism. RESULTS: AG was found to be safe up to 2000 mg/kg body wt., and it showed dose-dependent upsurge (p < 0.01 and p < 0.05, wherever necessary) in mount and intromission frequency, genital grooming, and anogenital sniffing at 150 and 300 mg/kg body weight suggesting aphrodisiac activity. In-vitro studies demonstrated significant relaxation of the Corpus Cavernosal Smooth Muscle at all concentrations in a dose-dependent manner. Furthermore, the results of molecular modelling studies were in agreement with the biological activity and showed interaction with phosphodiesterase-5 as a possible target. CONCLUSION: AG exhibited an aphrodisiac effect and substantiated the traditional claim of Indian ginseng-based ghrita formulation as 'Vajikarana Rasayana'.
Assuntos
Afrodisíacos , Withania , Animais , Feminino , Bovinos , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
In an attempt to improve the solubility and permeability of Standardized Bacopa Extract (SBE), a complexation approach based on phospholipid was employed. A solvent evaporation method was used to prepare the SBE-phospholipid complex (Bacopa Naturosome, BN). The formulation and process variables were optimized using a central-composite design. The formation of BN was confirmed by photomicroscopy, Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD). The saturation solubility, the in-vitro dissolution, and the ex-vivo permeability studies were used for the functional evaluation of the prepared complex. BN exhibited a significantly higher aqueous solubility compared to the pure SBE (20-fold), or the physical mixture of SBE and the phospholipid (13-fold). Similarly, the in-vitro dissolution revealed a significantly higher efficiency of the prepared complex (BN) in releasing the SBE (>97%) in comparison to the pure SCE (~42%), or the physical mixture (~47%). The ex-vivo permeation studies showed that the prepared BN significantly improved the permeation of SBE (>90%), compared to the pure SBE (~21%), or the physical mixture (~24%). Drug-phospholipid complexation may thus be a promising strategy for solubility enhancement of bioactive phytoconstituents.
Assuntos
Bacopa/química , Excipientes/química , Fosfolipídeos/química , Compostos Fitoquímicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Antidepressivos/administração & dosagem , Disponibilidade Biológica , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Masculino , Camundongos , Tamanho da Partícula , Permeabilidade , Difração de Pó , SolubilidadeRESUMO
In the present study, a phospholipid-based complex of standardized Centella extract (SCE) was developed with a goal of improving the bioavailability of its phytoconstituents. The SCE-phospholipid complex was prepared by solvent evaporation method and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy, and powder x-ray diffraction (PXRD) were used to confirm the formation of Centella naturosome (CN). The prepared complex was functionally evaluated by apparent solubility, in vitro drug release, ex vivo permeation, and in vivo efficacy studies. The prepared CN exhibited a significantly higher (12-fold) aqueous solubility (98.0 ± 1.4 µg/mL), compared to the pure SCE (8.12 ± 0.44 µg/mL), or the physical mixture of SCE and the phospholipid (13.6 ± 0.4 µg/mL). The in vitro dissolution studies revealed a significantly higher efficiency of CN in releasing the SCE (99.2 ± 4.7, % w/w) in comparison to the pure SCE (39.2 ± 2.3, % w/w), or the physical mixture (42.8 ± 2.09, % w/w). The ex vivo permeation studies with the everted intestine method showed that the prepared CN significantly improved the permeation of SCE (82.8 ± 3.7, % w/w), compared to the pure SCE (26.8 ± 2.4, % w/w), or the physical mixture (33.0 ± 2.7, % w/w). The in vivo efficacy studies using the Morris Water Maze test indicated a significant improvement of the spatial learning and memory in aged mice treated with CN. Thus, drug-phospholipid complexation appears to be a promising strategy to improve the aqueous solubility and bioavailability of bioactive phytoconstituents.
Assuntos
Centella/química , Fosfolipídeos/química , Fitoterapia/métodos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Envelhecimento/psicologia , Animais , Disponibilidade Biológica , Absorção Intestinal , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Percepção Espacial/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacocinéticaRESUMO
Pharmaceutical excipients are essential components of most modern dosage forms. Although defined as pharmacologically inert, excipients can be thought of as the true enablers of drug product performance. Unintentional variability in the properties of the excipients may be unavoidable, albeit minimizable. The variability may originate from the source, the excipient-manufacturing process, or during the manufacturing of dosage forms. Excipient variability may have a range of influences on their functionality and performance in the dosage form. A better understanding of these influences on the critical quality attributes of the final product is of prime importance. Modern analytical tools provide a significant assistance in characterizing excipient variability to achieve this understanding. The principles and concepts of Quality-by-Design, process analytical technology, and design space, provide a holistic risk-based approach toward manufacture and application of excipients in pharmaceutical formulations. The International Pharmaceutical Excipients Council (IPEC) has developed guidelines for proper selection, use, and evaluation of excipients in pharmaceutical products.