Objective: The study was aimed to improve the dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water-soluble drug.
Significance: Poor aqueous solubility of PGH was overcome by the design of SDs. Level A correlation demonstrated between in vitro release and bioavailability of PGH, suggest its biowaiver potential.
Methods: The effects of semicrystalline copolymers (poloxamer 407 and gelucire 50/13) and methods of preparations on dissolution behavior, in vivo performance, and stability of PGH SDs were investigated. All the SDs were characterized by FTIR, TGA, DSC, XRD, and SEM.
Results: FTIR and TGA showed the compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns & SEM indicated a change from a crystalline to an amorphous state. Gelucire 50/13 was observed to have greater ability to form SDs than poloxamer 407 in solvent evaporation method (SM). Prevention of recrystallization during storage suggested stability of the formulation. Gelucire 50/13 based SD, prepared by SM remarkably increased the dissolution within 15?min (87.27?±?2.25%) and was supported by dissolution parameters (Q15, IDR, RDR, % DE, f1, f2). These SDs showed pH-dependent solubility. In vivo test showed significantly (p?<?.05) higher AUC0–t and Cmax, which were about 3.17 and 4.34 times that of the pure drug respectively.
Conclusion: Gelucire 50/13 was found to be a suitable carrier for SM for preparation of SDs of PGH as evident from increased dissolution and bioavailability. 相似文献
The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel®) and hydrophobic (Compritol®) polymers. 32 full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel® and 8.21% w/w of Compritol® exhibited drug release pattern close proximal to the ideal theoretical profile (t50% = 5.92?h, t75% = 11.9?h, t90% = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel® and Compritol® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs. 相似文献
The study on the solvent extraction for quantitative and selective separation of total rare earth metals from the polymetallic nodule leach liquor was investigated. The typical leach liquor bearing 0. 094 g/L total rare earth, 0. 23 g/L Mn, 0.697 g/L Cu, 0.2 g/L Fe, 0.01 g/L Co and 0.735 g/L Ni was subjected to the removal iron content by precipitation method using Ca(OH)2 at pH 3.95, prior to solvent extraction of rare earth metals. Three different organo-phosphoric acid reagents(D2EHPA, PC88 A, Cyanex 272) were used to ascertain their performances and selectivity towards the loading of rare earth metals in presence of other base metals. Based on the results of eq. pH effect, the performances of above three extractants followed the order as: D2EHPA>PC88A>Cyanex 272. To ensure the absence of extraction of base metals(Cu, Co, Ni), the eq. pH of the solution was optimized at the level of 2.21, though higher rare earth metal extraction efficiency was observed at higher eq. pH with either of the extractants. The complete process flow diagram for substantial recovery of total rare earth was developed using D2 EHPA. Extraction isotherm plot was constructed at A:O=12:1, 3-stages and pHe=2.21, using 0.8 mol/L D2 EHPA and the predicted condition of this study was further confirmed by 6-Cycles Counter Current Simulation(CCS) study. The stripping of total rare earth from loaded organic phase(LO) was conducted using HCl solution. Mc-Cabe Thiele diagram study carried out at A:O=1:5 using 4 mol/L HCl showed that three theoretical stages were needed for quantitative stripping of total rare earth. The subsequent stripped solution resulted thus led to contain total rare earth of 5.6 g/L indicating a very high enrichment of total metals by solvent extraction(SX) process. 相似文献
Nuclear power plants contain a significant amount of fire load in form of electrical cables. The performance of the cables is interesting both from the fire development and system failure viewpoints. In this work, cable tunnel fires are studied using numerical simulations, focusing on the fire spreading along power cables and the efficiency of the water suppression in preventing the cable failures. Probabilistic simulations are performed using Monte Carlo technique and the Fire Dynamics Simulator (FDS) as the deterministic fire model. The primary fire load, i.e. the power cables are modelled using the one-dimensional pyrolysis model, for which the material parameters are estimated from the experimental data. Two different water suppression systems are studied. The simulation results indicate that using either suppression system decreased the heat release rate in the tunnel to less than 10% of the non-suppressed case. Without water suppression, the cables of the second sub-system were damaged in almost all fires, but when either of the studied water suppression systems was used, the probability of the cable failures was decreased to less than 1%. This result indicates that in current scenario, the probability of losing both sub-systems is determined directly by the suppression system unavailability. 相似文献
Background: Mucoadhesive drug delivery is a promising strategy to overcome ocular biopharmaceutical constraints. Objective and methods: Ciprofloxacin HCl-loaded reverse phase evaporation liposomes were coated with different concentrations and molecular weights of mucoadhesive biocompatible chitosan polymer to form chitosomes. This colloidal mucoadhesive system was evaluated in vitro and in vivo with respect to deliver the antibiotic to ocular surface. Results and conclusion: The results obtained pointed out that liposome coating process resulted in entrapment efficiency reduction and higher chitosan concentration, and molecular weight showed a more pronounced effect. No morphological differences between coated and uncoated liposomes were observed. Diffusion was the drug release mechanism from chitosomes. Concerning rheological behavior, pseudoplastic flow was characteristic to the prepared chitosomal dispersions. In addition, chitosan coating improved the ocular permeation of ciprofloxacin HCl. Microbiologically; this formulated system enhanced antimicrobial activity of ciprofloxacin HCl against both Gram-positive and Gram-negative bacteria. Moreover, this mucoadhesive system was able to inhibit the growth of Pseudomonas aeruginosa in rabbits' eyes for 24 hours when compared to the marketed preparation. In vivo bacterial conjunctivitis model elucidated that symptoms were controlled by the prolonged release formulation such as that done by the marketed product. 相似文献