Iranian Journal of Pharmaceutical Sciences

Cyclosporine (CsA) is a drug that has been used for prevention of kidney transplant rejection for many years. Diltiazem with the inhibition of cyclosporine metabolism and clearance will increase CsA concentration and CsA dose can be decreased. The aim of this study was the evaluation of diltiazem effect on CsA dose adjustment with respect to C2. Forty stable renal transplant patients who were
receiving CsA, prednisolone, mycophenolate mofetile as well as diltiazem were enrolled in the study. At first, minimum concentration of CsA (C0) and concentration within 2 h after dosing (C2) were determined in every patient. These patients were randomly assigned to an 8-week period of continued therapy with diltiazem (20 patients), or to a washout period removing diltiazem from the treatment (20 patients).
At the end of this period, CsA concentrations were measured. Thereafter, the groups underwent a crossover followed by either diltiazem washout or reinstituted treatment with diltiazem. Then C0 and C2 were measured. In each step which diltiazem was removed from patient drug regimen, CsA dose was increased by 25%. Finally, we detected that this amount of CsA dose adjustment is suitable in our patients and C0
and C2 remained in the therapeutic windows. Diltiazem co-administration with CsA will be safe and cause decreased patients drug cost.

In order to enhance in vitro dissolution and content uniformity of poorly soluble drug glimepiride by preparing solid dispersions using modified solvent fusion method, solid dispersions of drug were prepared by modified fusion solvent method using PEG 6000 and PVP K25 (as carrier). Eight batches (F1-F8) were prepared by Factorial design (23) by taking three factors i.e. the concentration of: drug (X1), PEG
6000 (X2) and PVP K25 (X3). DSC, FTIR spectroscopy, powder X-ray diffraction (XRD) and SEM studies were used to characterize solid dispersions. In vitro release was carried out using USP II dissolution apparatus. Multilinear regression analysis was applied to develop mathematical model to estimate cumulative drug release. The batch F3 was found to be best batch as it showed maximum in vitro dissolution
after 30 min. Improvement in dissolution behavior of solid dispersion batches was observed due to conversion of crystalline form of drug to amorphous form as confirmed by DSC, FTIR studies and X-RD studies. SEM photographs of batch F3 showed porous nature of particle surface. Uniformity of content of different batches was found to be in range as specified by IP. Solid dispersion prepared via modified
fusion solvent method was proved to be beneficial in enhancement of dissolution rate of poorly-water soluble drug using hydrophilic carriers. Retrospectively, this model can further be utilized to design solid dispersions for desired release characteristics.

The Extended Hildebrand Solubility Parameter Approach (EHSA) is used to estimate the solubility of satranidazole in binary solvent systems. The solubility of satranidazole in various water-PEG 400 mixtures was analyzed in terms of solutesolvent interactions using a modified version of Hildebrand-Scatchard treatment for regular solutions. The solubility equation employs term interaction energy (W) to replace the geometric mean (δ1δ2), where δ1 and δ2 are the cohesive energy densities for the solvent and solute, respectively. The new equation provides an accurate prediction of solubility once the interaction energy ‘W’ is obtained. In this case, the energy term is regressed against a polynomial in δ1 of the binary mixture. A quartic expression of ‘W’ in terms of solvent solubility parameter was found for predicting the solubility of satranidazole in water-PEG 400 mixtures. The expression yields an error in mole fraction solubility of ~2.17%, a value approximating that of the experimentally determined solubility. The method has potential usefulness in preformulation and formulation studies during which solubility prediction is important for drug design.

The present study was performed to explore the matrix property of Ficus glomerata fruit mucilage for making transdermal patches. The mucilage was evaluated for its physicochemical properties. Various transdermal patches of indomethacin were prepared by solvent evaporation technique using different proportions of F. glomerata fruit mucilage. The compatibility studies between indomethacin and F. glomerata fruit mucilage revealed that there were no negative interactions between indomethacin and the mucilage. The formulated patches were evaluated for physical properties, pre-formulary, post-formulary and skin irritation characteristics and they were found satisfactory. The experimental results shows that the drug release from the patches delayed in controlled manner as the proportion
of F. glomerata fruit mucilage increased. The accelerated stability studies proved that the formulated patches were stable at stressed storage conditions. It was concluded that F. glomerata fruit mucilage can be used as polymer for making transdermal patches.

In the present work, the effect of Ca(NO3)2.4H2O and (NH4)2HPO4 primary solutions as the beginning materials in synthesis of a calcium phosphate phase, was examined. So, we investigated the wet chemical reactions in solution at different temperatures by a hydrothermal condition aimed at hydroxyapatite (Ca10(PO4)6(OH)2); (HAp) synthesis. The powders were investigated by XRD, SEM, FE-TEM, HRTEM, EDAX, SAED and FT-IR. It was found that HAp has a length of approximately several micrometres and a diameter of 20-30 nm with different morphologies. As a matter of fact, the method of hydrothermal method
guarantees the production of HAs for different applications especially clinical applications.

Nitric oxide (NO) is an important molecule synthesized during wound repair. Studies have reported the use of NO donors on cutaneous wound repair, but their effects in different phases of healing are not elucidated. The aim of this work was to investigate the effects of topical sildenafil on wounds in rats. Sildenafil (25 mg) was topically applied once daily on wound in treatment groups. On days, 7, 14 and
21 of lesion, five animals in each group were randomly selected and sacrificed and histological properties were evaluated. Our results showed the wound area contracted to 15% of the original size by day 7 post-wounding in treated group. Whereas control rats showed significantly delayed wound healing. The wound area contracted to 26% of the original size by day 14 post-wounding and to 46% by day 21 post-wounding. Also sildenafil cream caused more fibroblast and macrophage migration, increased vascularization, collagen regeneration, and epithelialization. This study indicates that sildenafil cream augments the wound healing process and may be of clinical benefit.

The crude methanolic extract of the seeds of Celastrus paniculatus along with its organic soluble fractions were tested for their possible antioxidant and antialzheirmer (AD) activity. The extracts showed prominent DPPH free radical scavenging activity, inhibiting activity of authentic peroxynitrite (ONOO-) and inhibition of total reactive oxygen species (ROS) generation. In DPPH radical scavenging assay, the EtOAc fraction showed the highest activity with a IC50 value of 25.92±1.02 μg/ml whereas aqueous fractions had no activity at all within the tested concentration. Scavenging of the authentic ONOO- system, all
extract/fractions showed good activity and among them, EtOAc fraction had the highest activity with a IC50 value of 15.79±0.18 μg/ml. EtOAc fraction also showed significant (p<0.001) inhibitory activity against the total ROS generation which was almost similar with that of the positive control Trolox (IC50 16.79±0.19 μg/ml). All extract/fractions exhibited statistically significant (p<0.001) cholinesterases (ChEs) inhibitory effects with IC50 values ranging between 134.7-227.5 μg/ml for AChE and 209.6-562.1 μg/ml for BChE.

The purpose of this study was to develop a sensitive and fast microdialysis coupled with high-performance liquid chromatographic (HPLC) method for determination of 5-hydroxymethyl-2-furaldehyde (5-HMF) in free-moving rats after i.g. administration of the aqueous extract of crud Fructus corni and its processed products of jiuzheng pin (JZP). The concentration of 5-HMF in free-moving rats after i.g. administration of the water extract of Fructus corni and JZP was analyzed by microdialysis coupled with HPLC. Results demonstrated that the concentration of 5-HMF in microdialysate was 1.4951μg/l, but higher in rat microdialysate after i.g. administration of the aqueous extract of JZP (5.2662 μg/l). In conclusion, this method is proved to be rapid，accurate and simple. Real-time in vivo monitoring the concentration of 5-HMF provides the theoretical basis for further explaining the processing mechanism of F. corni.