Improvement of solubility and dissolution rate of indomethacin by solid dispersions in gelucire 50/13 and PEG4000

The aim of this study was to prepare and characterize solid dispersions of water insoluble non steroidal anti-inflammatory drug, indomethacin [IND], with polyethylene glycol 4000 [PEG4000] and Gelucire 50/13 [Gelu.] for enhancing the dissolution rate of the drug. The solid dispersions [SDs] were prepared by hot melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron microscopy [SEM], X-ray powder diffractometry [XRD] and differential scanning calorimetry [DSC] were used to examine the physical state of the drug. Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The data from the XRD showed that the drug was still detectable in its solid state in all SDs of IND-Gelu and disappeared in case of higher ratio of IND-PEG4000. DSC thermograms showed the significant change in melting peak of the IND when prepared as SDs suggesting the change in crystallinity of IND. The highest ratio of the polymer [1:4] enhanced the drug solubility about 4 folds or 3.5 folds in case of SDs of IND-PEG or IND-Gelu., respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed when the drug was dispersed in these carriers in form of physical mixtures [PMs] or SDs. IND released faster from the SDs than from the pure crystalline drug or the PMs. The dissolution rate of IND from its PMs or SDs increased with an increasing amount of polymer

Preparation, in-vitro release and anti-inflammatory activity of meloxicam in different gel formulations

This study was designed to evaluate different polymers to their suitability for formulation as vehicles for topical delivery system. Meloxicam [MX] was incorporated into the gel vehicles in a concentration of1.0% w/w. It is a non-steroidal anti-inflammatory drug [NSAID] of the enolic acid class of compounds. Polymers used in this study are methylcellulose [MC], tylose [Ty], polyvinyl alcohol [PVA], poloxamer 407 [polo], polyethylene glycol [PEG], carbopol 974P [Carb. And eudispert mv. [Eud]. They are used in a suitable concentration for gel formation. In-vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer ph 6.8. The release data were treated with various kinetic principles to assess the relevant parameters. The general rank order of MX release was MC > Ty > polo > PVA> other gel forms. The results also showed that, the release of drug from the prepared gels obeyed the diffusion model [Higuchi's equation]. The influence of some formulation and processing variables [initial drug concentration of 0.5, 1.0 and 2.0% w/w, poloxamer 407 concentration of 20, 25, 30% w/v in the aqueous gel formulation] on the release patterns have been studied. The results revealed an inverse correlation between the drug release rate and the poloxamer 407 concentration and direct correlation between the drug release rate and the initial drug concentration. The anti-inflammatory activity of the drug in different gel formulations was studied using carrageenan induced rat paw edema method. The results obtained show an excellent anti-inflammatory activity on rat paw edema

Preparation and comparative evaluation of sustained release metoclopramide hydrochloride matrix tablets

Metoclopramide hydrochloride [MCP] is commonly used for the management of gastrointestinal disorders. Frequent administration and the undesired side effects [extra pyramidal symptoms] of the drug on the central nervous system due to the fluctuations of its plasma concentrations may lead to patient incompliance, and hence, improper therapy. Therefore, the present work will be devoted to formulate the drug in sustained release formulations. MCP was incorporated in 12 formulae containing different polymers and/or different polymer ratios. These polymers were hydroxypropylmethyl cellulose [HPMC], carboxymethylcellulose [CMC] and ethyl cellulose [EC]. Sodium starch glycolate [SSG] was added to some formulae in different amounts in order to soften and/or disintegrate the tablets. The physical properties were found to be satisfactory for all the formulae. The dissolution profiles of the tablets were constructed using the change-over method. The drug release involved a combination of both diffusion and polymer-chain relaxation mechanisms. The time required to release 50% of MCP ranged from 1.2 to more than 8 hours. Direct compression and dry granulation techniques produced sufficient sustaining of the drug release. However, the pellets made by wet granulation released MCP in about 2 hrs, i.e., Pelletization spheronization technique was not effective in sustaining the drug

Preparation and characterization of albendazole microparticles prepared by freeze-drying technique

The aim of this work is preparation of albendazole [ABZ] micro particles with certain hydrophilic polymers such as hydroxypropyl methylcellulose [HPMC], and polyvinyl pyrrolidone [PVP] using freeze- drying technique. Microparticles of ABZ with these polymers were prepared in different ratios of 1:1, 1:2, and 1:4. Morphology of the prepared ABZ microparticles was studied using a scanning electron microscope. Spherical microparticles with smooth surface of ABZ were detected by this method. Physicochemical properties of drug alone and its freeze-dried microparticles were investigated using differential scanning calorimetry [DSC] and powder X-ray diffractometry [PXRD]. DSC and PXRD analysis showed that ABZ was transformed from the crystalline state to amorphous state by freeze- drying with the chosen polymers as confirmed by disappearance of its melting peak and characteristic crystalline peaks. Dissolution rate of ABZ from the prepared micropartides was determined and compared to its corresponding physical mixtures. Results showed that, the dissolution of freeze-dried micropartides was faster than the corresponding physical mixtures and drug alone. This indicates that, the freeze-drying technique improved ABZ dissolution. Moreover, it was found that the dissolution rate of the drug was affected by the polymer type and the ratio of ABZ to polymer

Liposomal gel of diclofenac sodium as topical delivery system

This study the preparation of diclofenac sodium in lecithin vesicles and loading in pluronic F-127 gel, the effect of sodium cholate on the diffusion of the drug through rat skin and the anti-inflammatory activity of the liposomal gel formulations. Lecithin vesicles were prepared in the presence or absence of sodium cholate by the dry film method and sonication. The size of liposomal vesicles ranged from 100-700 nm and the encapsulation efficiency of the diclofenac sodium was between 60-80%. The lecithin vesicles were loaded in pluronic F-127 gel. The highest cumulative of drug diffusion through rat skin was 19.31 +/- 1.50 [micro g/cm[2]] for lecithin vesicles in the presence of sodium cholate [F4]. Also the highest cumulative of drug diffusion through rat skin was 12.20 +/- 0.50 [micro g/cm[2]] for liposomal gel [F8]. The anti-inflammatory activity of the liposomal gel formulations was studied on carrageenan induced paw edema in rats. The results show that, F8 and F6 show superior anti-inflammatory activity in comparison with the other gel formulations. From the results, lecithin vesicles and liposomal gel of diclofenac sodium appear to be advantageous for topical delivery of the drug

Spray-dried HPMC Microparticles of Indomethacin: impact of drug-polymer ratio and viscosity of the polymeric solution on dissolution

Polymeric microparticles prepared by spray-drying technique were investigated to enhance the dissolution rate of indomethacin [IM] in comparison with conventional microparticles prepared by co-precipitation solid dispersion method. Drug-polymer ratios and viscosity of polymeric solutions as potential factors were used in order to enhance the dissolution rate of IM. Spray-drying technique was used for preparing of microparticles using aqueous suspension of IM in hydroxypropyl methylcellulose [HPMC] polymer solution. The effect of drug-polymer ratios on dissolution rates of IM was studied in simulating intestinal medium. IM was analyzed spectrophotometrically at lambda=320 nm. For each drug-polymer ratios, low and high viscosity polymeric solutions were prepared and their impacts on the dissolution of IM were observed. Microparticles were morphologically characterized by optical microscopy. The interaction between IM and HPMC was studied by differential scanning calorimetry [DSC] and x-ray diffractometry [XRD]. Spherical fluffy microparticles of IM were obtained using HPMC. It was observed that the prepared spray-dried microparticles significantly increase the dissolution rate of IM. The increase in dissolution rates was achieved with drug: polymer ratios 1:1 as well as 1:2 and interestingly, the decrease in drug content in ratio exceeding 1:2 resulted in reduction in dissolution rates. Also, with all drug-polymer ratios, the low viscosity polymeric solutions gave the higher dissolution rates. In conclusion, HPMC microparticles loaded with IM were prepared by spray-drying technique and the potential of this technique to enhance the dissolution was studied. The findings indicate that the dissolution profile of IM microparticles prepared by spray-drying technique relied on drug-polymer ratios and viscosity of polymeric solutions

Nitric oxide synthase gene polymorphism and in-stent restenosis: clinical and angiographic follow-up

Coronary stent deployment is a major advance in the treatment of ischaemic heart disease, but angiographic in stent restenosis still occurs in 10-40% at 6 months due to neointimal hyperplasia. Patient specific factors, including genetic factors, can contribute to this process. Was to examine the 894 G/T single nucleotide polymorphism [SNP] of the endothelial nitric oxide synthase [eNOS] in causing adverse angiographic and clinical events after coronary artery stenting. Our study included 47 patients [40 males, 7 females, mean age 54.4 +/- 8.1] who underwent elective and successful coronary artery stenting to de novo lesions in the Critical Care Department [Cairo University]. Patients were followed up for major adverse cardiac event [MACE] defined as death, acute coronary syndromes and target vessel revascularization; and restudied by coronary angiography at 6 months. The stented lesions were assessed using an automated quantitative angiography system. Genotype was determined by real time polymerase chain reaction [PCR] and restriction enzyme digestion. Restenosis rate was defined as >/= 50% diameter stenosis. The pts were distributed into two groups, Group linvolved pts of the G allele carriers i.e. patients of genotype PG or GT [n=40] and group II consisting of patients genotype IT, which represented the proposed risk genotype [n=7]. Patients in group I showed greater prevalence of diabetes mellitus [DM] and greater severity of lesions. Patients with GGIGT genotype presented with higher incidence of acute coronary syndromes compared to patients with TT genotype [45% vs 14.3%, p: 0.004]. The same genotype group had significantly higher incidence of MACE [45% compared to 28 0.001]. Patients with TI' genotype had insignificantly higher restenosis rate [42.9% in comparison to 37.5% in group GG/GT genotype, p: 0.8]. Although GG/GT genotype showed higher incidence of acute coronary syndromes and MACE compared to patients with TI genotype, yet the latter had in significantly higher restenosis rate

Primary versus delayed PCI after acute MI: effect on ventricular remodeling and function

It has been well established that early restoration of patency of IRA by percutaneous coronary intervention [PCI] with recent myocardial infarction [MI] may preserve left ventricular [LV] global function and also prevent LV remodeling. There were controversies however concerning the possible benefits of delayed [within 30 days] restoration of patency of infarct-related artery of patients. To evaluate and compare the results of primary versus delayed PCI in patients with acute MI. Forty patients [35 males, 5 females mean age 50.9] were included in the study with first anterior MI, and were divided into 2 groups. Group A[20 pst] who had the chance of undergoing primary PCI within a mean 5.4 hrs from the onset of chest pain with a door to balloon time 1.6 hrs and group B[20pts] with delayed hospitization [i.e>12 hours] who nether received thrombolytic nor primary PCI, but were scheduled for routine PCI with a mean of 20.7 days. The LV function and dimensions were assessed by serial echocardiographic readings measuring LV end diastolic volume [LVEDV], LV end systolic volume [LVESV], ejection fraction [EF], regional wall motion scoring index [RWMI] at 24hrs of admission and after 3 and six months. At 3 months compared to delayed PCI group, group showed significant improvement in RWMI [from 1.9 +/- 0.3 to 1.27 +/- 0.13 in group A vs 1.6 +/- 0.2 to 1.38 0.18 in group B, p value 0.032]. There was a non significant increase in LVEDV values in the two groups, [from 101 +/- 17.6 to 109 +/- 20.1 in group A vs 98.3 +/- 22.3 to 106.3 +/- 22.1 in group B, p 0.062]. The change in EF values was nearly the same in both groups; [59.6% +/- 3.9 at base line to 58.5% +/- .5 in group A vs 57.1%9.3 to 55.2% +/- 6.4 in group B]. At six month, there was no more improvement in the RWMI in both groups but the group B showed marked increase in LVEDV [from 98.3 +/- 22.3 at base line to 138 +/- 32.96, i.e. 28.9% increase versus 15% increase in the group A [from 101 +/- 17.6 at base line to 115 +/- 32.14, p=0.041]. Where the EF% value was nearly preserved in group A [59.6% +/- 3.9 at base line to 59.9% +/- 6.81], there was remarkable deterioration in the EF% in the delayed group [from 57.1 +/- 9.3 at base line to 51.8 +/- 10.8, p 0.008] after six month. Despite the enthusiasm to the concept of restoring patency of infarct related artery irrespective of time, our data showed that early and immediate revascularization [primary PCI] is superior to delayed intervention. Therefore prompt restoration of patency is highly recommended for myocardial salvage and preserving LV function

Ibuprofen-quercetin combination as a novel pharmaceutical compatible system

The effect of oral administration of quercetin [QRT] [25 mg/kg] on an experimentally Ibuprofen-induced ulcer was studied in rats. The results of gross appearance and scanning electromicrographs of the mucous membrane and superficial cells of the stomach revealed that the quercetin reduced the damage of submucosal superficial cells. Differential scanning calorimetry, X-ray diffractometer, IR spectroscopy, solubility and partitioning studies elucidated the absence of any interaction between the two compounds and also the physical compatibility of ibuprofen [IP]-quercetin combination. It is concluded that ibuprofen and quercetin can be pharmaceutically co-formulated or co-administrated with the aim of reducing the gastrointestinal adverse effects of ibuprofen