Home > Preparation, Characterization, in Silico Modelling and Bioavailability of Nanosuspention for Poorly Water Soluble Drugs Dexibuprofen and Domperidone
Preparation, Characterization, in Silico Modelling and Bioavailability of Nanosuspention for Poorly Water Soluble Drugs Dexibuprofen and Domperidone
The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) and domperidone nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method (APSP). Combinations of Hydroxypropyl methyl cellulose-Polyvinyl pyrrolidone and Hydroxypropyl methyl cellulose-Eudragit were shown to be very effective in producing stable dexi-nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179± 0.01, 0.182± 0.02 respectively. Produced nanocrystals of DOMP and Ethucel combination, the average particle size and polydespersity index were found to be approximately 130.00 ± 3.0 nm, 0.15 ± 0.01, moreover, the combination of hydroxyl propyl methyl cellulose and polyvinyl alcohol also found very affective to produce DOMP nanocrystals with small particle size (200.0 ±3.5nm) and PDI (0.2±0.02). The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2-8°C and 25°C were more stable than those at 40°C. The maximum recovery of dexi-nanocrystals was observed from the formulations using the combination of Hydroxypropyl methylcellulose- Polyvinyl pyrrolidone and Hydroxy propyl methyl cellulose- Eudragit, which equated to98% and 94% of the nominal active drug content respectively. In case of DOMP nanosuspensions stored at 2-8 ºC and room temperature (25 ºC) exhibited higher stability compared to the samples stored at 40 ºC. Crystallinity of the processed and unprocessed dexi and DOMP particles was confirmed using Differential Scanning Calorimetry, Powdered X-ray Diffraction and Transmission Electron Microscope. FTIR studies for both Dexi and DOMP nanocrystals confirmed that the process did not affect chemical integrity of DOMP. The DOMP nanoparticles exhibited significantly enhanced dissolution rate (P<0.05) compared to the raw counterpart. The saturation solubility of the ix dexinanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw dexi in water (51.0± 2.0μg/mL) and stabilizer solution (92.0 ± 3.0 μg/mL). Enhanced dissolution rate (P<0.05) was observed for the dexi-nanocrystals compared to the unprocessed drug substance and marketed tablets. The saturation solubility of the DOMP nanocrystals was significantly increased to 2700.0± 3.5 µg/mL compared to the raw dexi in water (952.0± 2.0μg/mL) and stabiliser solutions which include HPMC (1253.0± 3.5) and HPMC-PVA (1133.0 ± 3.5 µg/ml). DOMP nanocrystals resulted in enhanced dissolution rate (P<0.05) compared to the unprocessed drug substance. Molecular Modeling studies underpinned and substantiated the experimental studies, including the impact of polymers on nanoparticle sizes, nanocrystals recovery and stability studies of the produced dexinanocrystals. The highest potential was shown by combination ofHPMC-PVP- Dexi (-4.7) and HPMC EUD- DEXi (-4.6) . In case of DOMP, Molecular Modelling studies underpinned the molecular level understanding of the DOMP-Polymer nanocrystal interaction and substantiated the experimental studies, including the impact of polymers on nanocrystals sizes, and stability studies of the produced DOMP nanocrystals. Ethocel as single polymer showed highest binding potential (-27.26±0.24 ) for DOMP nanocrystals and HPMC-PVA was found the best dimer to effectively bind (-25.22 ± 0.79) with the nanocrystals with subsequent small particle size and high stability profile. The findings of the nociceptive assay showed that the dexinanocrystals exhibited significant analgesia, compared to the raw dexibuprofen and the control standard diclofenac sodium. The analgesic effect was, however, produced at much lower doses (5mg/kg) than that of control standard, diclofenac sodium (20mg/kg) and dexibuprofen counterparts (40 mg/kg). While theactivity results in anti-emetic assay confirmed that the nano-formulation provided significant anti-emetic effect (P< 0.05) x at a dose of 0.5 mg/kg, comparable to that of the unprocessed DOMP and the control standard Metoclopramide administered at the doses of 1.0m/kg and 30mg/kg respectively. However, DOMP nanoparticles showed the anti-emetic effect at lower doses compared to that of control standard and unprocessed DOMP. Furthermore, there was observed a substantial % increase of antiemetic potential for DOMP nanoparticles compared to the unprocessed DOMP and the standard metoclopramide.
جدوں اویس دا ٹُٹا دند ہوئے حضوری وچ پسند رہن عاشق توں پاسے پاسے ہور نہیں دیندے کوئی گزند عشق توں رہندے دور دراڈے جیہڑے بندے عقل مند سوہنے ڈگدے سوہنیاں اتے کر کے ساڈا ساہ بند ہمدردی تے خدمت سیوا ایہو نیکاں دی ہے ، ھند دکھاں درداں دے جو ساتھی دنیا اتے بندے چند ڈرے حنیف خدا توں خبرے کیہڑا اوہنوں رنگ پسند
The aim of this analysis was to ascertain the degree to which the Head of the Integrated Business Services Office's Leadership Style affects the efficacy of the Integrated Business Services Office's management. In data analysis, a descriptive study of one variable was performed to determine the percentage trend of each test variable; second, the commodity moment correlation formula was used to analyze variable relationships; and third, a basic equation model was used to analyze the impact relationship between the independent and dependent variables. The data for this study were processed using a micro statistical program with the assistance of a computer program. The data analysis and interpretation of the study's hypotheses indicate that there is a significant relationship and influence between the variable leadership style of the Integrated Business Services Office's Head and the effectiveness of the Integrated Business Services Office's management, at the 5% significance level or P = 0, 05, respectively.
Field application of dairy manure is supposed to alter rates of nitrogen mineralization in to nitrate nitrogen in soils but quantitative information regarding its rate of release under deficit irrigation is difficult to assess under filed conditions. To address this issue of great concern field and laboratory studies were conducted to assess its rate of release under field conditions and in lysimeter under controlled conditions. Incubation study was performed to assess nitrogen mineralization into nitrate and ammonium form under different levels of moisture (50, 60, 70, 80, 90 and 100% of FC). A lysimeter trial was conducted using optimized levels of deficit irrigation (I0.6 and I0.8) and full irrigation (I1.0) along with four levels of dairy manure (10, 15, 20 and 25 Mg ha-1) to assess best combinations of manure and deficit irrigation. Solution samplers already installed at 30, 60, 90 and 120 cm depths in lysimeter were used for leachate collection. Two year field study was conducted using best combinations of deficit irrigation and dairy manure (I0.6DM20, I0.6DM25, I0.8DM20, I0.8DM25) along with three levels of nitrogen fertilizer (80, 100 and 120 kg ha-1). Soil sampling was done before sowing and after crop harvest for the analysis of mineralized nitrogen (NO3 and NH4), soil chemical and biological indicators like soil organic carbon, pH, total N, available P and K. Soil physical health indicators viz. bulk density (BD), total soil porosity (TSP), infiltration rate (IR), soil strength (SS) and hydraulic conductivity (HC) were determined. Manure application at 25 Mg ha-1 increased the yield of wheat by 35% under lysimeter. Manure showed additional advantage on soil health indicators, i.e. higher SOC contents, IR, HC and TSP and decreased BD and SS. Application of dairy manure at the rate of 25 Mg ha-1 under deficit irrigation (I0.8) resulted in grain yield equivalent to that under 100% FC and improved soil physical health. Application of high rates of dairy manure resulted in more nitrate leaching at 120 cm under full irrigation, while under deficit irrigation leaching occurred above critical limit only up to 60 cm soil depth. Results concluded that deficit irrigation level I0.8 has shown best results with DM25 and N120 on wheat crop yield and soil health indicators with minimum nitrate nitrogen leaching losses.