Formulation and in-vivo study of ketoprofen tablets prepared using chitos an interpol ymer complexes

The application of interpolymer complexes [IPCs] for oral controlled drug delivery systems was tested between chitosan and various anionic polymers viz sodium alginate, sodium carboxymethylcellulose and pectin. The prepared IPCs were investigated using Fourier transform infra-red spectroscopy and differential scanning calorimetry, Ketoprofen tablets were prepared using the polymers alone, physical mixtures of chitosan with sodium alginate, sodium carboxymethylcellulose or pectin in different ratios; 1:3, 1:1 and 3:1, and the corresponding IPCs. In-vitro release studies were carried out in two dissolution media; 0.1 N HCl ofpH 1.2 and phosphate buffer ofpH 7. 4. It was found that, chitosan - sod. carboxymethylcellulose 1PC tablets showed more controlled drug release compared to that containing chitosan - sodium alginate and chitosan -pectin IPCs. The dissolution rate from tablets prepared using physical mixtures of polymers were found to be dependant on the interaction between chitosan and each of the anionic polymers in the physical mixtures, their ratios and pH of the dissolution medium. Tablets prepared using chitosan - sod. carboxymethylcellulose physical mixture 1:1 and chitosan - sod. carboxymethylcellulose IPC were selected for the in-vivo study using albino rabbits. The results showed a lower peak plasma concentration and marked controlled release effect of drug in tablets containing the physical mixture compared to that of the IPC and the control tablets

Effect of penetration enhancers on the permeability of ketoconazole gels through rabbit skin

The influence of several penetration enhancers on the percutaneous penetration of ketoconazole [KC] from hydroxypropylmethyl cellulose [HPMC], sodium carboxymethyl cellulose [NaCMC] and carbopol 934 gel formulations was investigated. Skin permeation studies were performed using Franz-type diffusion cells and full-thickness abdominal rabbit skin. Various types of compounds such as oleic acid [OA], menthol [M] and isopropyl myristate [IPM] in various concentrations were employed as penetration enhancers. The steady-state flux, permeability coefficients, and enhancement ratios ER of [offlux] KC for each formulation were calculated. The results showed that the skin permeability of KC from gels tested was significantly increased [P< 0.05] by 10% w/w OA, 5% w/w M and 5% w/w IPM. ER [flux] of KC gels containing 10% OA were 19.5, 16.4 and 11.9 for NaCMC, HPMC and carbopol gel respectively. ER [flux] of 5% w/w M were 13.5, 13.3 and 10.9 for HPMC, NaCMC and carbopol gel respectively. About 11 fold increase in the ER [flux] at 5% w/w IPM for all gels. Kinetic analysis of the data indicated that the permeation of [KC] from different gel formulations obeyed Higuchi-diffusion model. In conclusion, OA, M and IPM could be considered as penetration enhancers for KC topical formulations

Assessment of toxicological effects and persistence of the fungicide Zineb in laying hens

Zineb, a fungicide of ethylenebisdithiocarbamate group, is widely used as a protective fungicide in agriculture purposes. The present work was carried out to assessment the toxicological effects and the fate of "zineb" in laying hens. Zineb and some of its degradation products have been prepared in our laboratory for the present investigation. Hens were treated with 50 and 100 ppm of zineb in the feed for two months followed by one month recovery period. At the end of the experimental period, both plasma and red blood cells [RBCs] - cholinesterase activities showed a moderate inhibition amounting to [24.4 and 31.0% for plasma and 8.0 and 10.5% for RBCs at two treated doses [50 and 100 ppm], respectively. Liver and kidney functions as well as lipid profile of the treated hens were increased, while concentration of total protein and albumin were decreased during the experimental period. All the blood parameters returned to control values after a one month recovery period except lipid parameters [Cholesterol and triglycerides]. The residual analysis of the extracts of whole eggs, blood and different organs of laying hens revealed that, a considerable amount of the parent compound was detected and amounted to, whole eggs [0.171 and 0.322 ppm], fat [0.071 and 0.135 ppm], liver [1.11 and 2.05 ppm], muscles [0.385 and 0.650 ppm], whole blood [0.160 and 0.305 ppm] and heart [0.155 and 0.270 ppm] for both doses [50 and 100 ppm], respectively at the end the experimental period. Chromatographic analysis by TLC and HPLC of the extracts of whole eggs, blood and different organs of laying hens showed the presence of five degradation products in addition to the parent compound zineb

Phonophoresis of theophylline through cellophane membrane and rabbit skin

The influence of ultrasound waves upon the permeation of theophylline through cellophane membrane and rabbit skin was studied in vitro. Sonication was carried out with continuous mode at intensities [0.5, 1, 1.5, and 2 W/cm 2 at constant frequency 800 KHz for one sr. Different gel formulations with [hydroxypropylmethyl cellulose, sodium carboxymethylcellulose and carbopol 934P] in different concentrations [1-4% w/w] were utilized. Phonophoresis of theophylline through rabbit skin were significantly less than that obtained with the cellophane membrane. Ultrasound application has showed a significant increase in the amount of theophylline permeation with increasing intensity. For all the tested gelling agents, the amount of drug released was decreased by increasing polymer concentrations. The Flux values were 5.99, 3.69 and 2.4 [micro g/min cm 2] for 2% HPMC, 4% Na CMC and 2% carbopol 934P gels respectively. It was found that drug release from HPMC gels obeys Zero-Order model while its release from Na CMC and carbopol 934P were fitted with First-Order and Higuchi-diffusion model respectively

Toxicological potential and the fate of the insecticide chlorpyrifos in laying hens

The present study was conducted to investigate the toxicological effect and the fate of the insecticide chlorpyrifos in laying hens. Chlorpyrifos and some of its degradation products have been prepared in our laboratory for the present investigation. Hens, were fed 40 ppm of chlorpyrifos in the feed for two months followed by one month recovery period. After 30 days of the experiment, both plasma and red blood cells-cholinesterase activity showed a moderate inhibition amounting to 32.4 and 17.9%, respectively. Liver and kidney functions as well as lipid profile of the treated hens were significantly increased during the experiment periods. All the blood parameters returned to the control values after one month recovery period except liver enzymes [ALT, AST and alkaline phosphatase]. The residual analysis of the extracts of both eggs and different organs of laying hens revealed that, there was a considerable amount of the parent compound which amounted to: eggs [0.02 ppm], fat [0.095 ppm], liver [0.093 ppm] and muscles [0.007 ppm] at the end the experiment. Chromatographic analysis by TLC and HPLC showed the presence of four degradation products in addition to the parent compound chlorpyrifos

Influence of ginger [Zingiber officinales Rosc] on chronic toxicity induced by the organophosphorus insecticide "chlorpyrifos" in laying hens

Pesticides may induce toxic symptoms and alteration of most blood enzymes in experimental animals. Ginger rhizome [Zingiber officinales] is one, of the best known spices, which has also been universally used throughout history for its health benefits. For evaluation of the toxic effect of subchronic exposure to chlorpyifos, the protective effect of ginger rhizome, an indigenous medicinal plant was studied through estimation of different blood parameters at different time intervals. These blood parameters are the red blood cells [RBCs] and plasma cholinesterase activity, liver and kidney functions, level of cholesterol and triglycerides as well as the main metabolites of chlorpyrifos in laying hens. Administration of diet contaminated by chlorpyrifos at a dose of 40 ppm for two months followed by one month recovery period led to a slight inhibition of RBC and plasma cholinesterase and significantly increased the activity of liver enzymes, namely alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] activities. Total protein and albumin were slightly decreased and serum creatinine and blood urea were significantly increased. Cholesterol and triglycerides were slightly increased. The main metabolites detected in the extracts of eggs and different organs of laying hens were 3, 5, 6-Trichloro-2-hydroxypyridine, chlorpyrifos oxon, desethyl chlorpyrifos and desethyl chlorpyrifos oxon, in addition to the parent compound, which were identified and confirmed by tic and hplc. Feeding hens on a diet containing dursban at a dose of 40 ppm and Zingiber officinales Rose [ginger 1%, w/w], significantly ameliorate the toxic effect of chlorpyrifos. This results indicate the possible chemoperventive action of ginger and emphasize the potential of natural plant products as chemopreventive agents

Evaluation of ginger effect on induced chronic toxicity by the dithiocarbamate fungicide "Zineb" in laying hens

Ginger rhizome, an indigenous medicinal plant, has a long history of both culinary and medicinal use in a Chinese, Japanese and Indian medical care. The protective effect of ginger on induced chronic toxicity by the dithiocarbamate fungicide "Zineb", was studied in laying hens through the estimation of different blood parameters at different time intervals. These blood parameters are, cholinesterase activities of both red blood cells [RBCs] and plasma, liver and kidney functions, level of cholesterol and triglycerides as well as residue levels and the main metabolites of zineb in laying hens. The obtained results showed that administration of diet treated with zineb at a dose of 100 ppm for two months followed by one month recovery period led to a slight inhibition of RBCs and plasma cholinesterase activities and to a slight decrease in total protein and albumin content. On the other hand, zineb toxicity increased serum creatinine, blood urea, total cholesterol and triglycerides levels. In addition, liver enzymes, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP] activities showed moderate increase in the zineb treated group. The main metabolites detected in the extracts of different organs, blood and whole eggs of laying hens in group I were, ethylene thiourea, ethylene thiuram monosulifde, ethylene thiuram disulfide, ethylene urea, Jaffe's base in addition to the parent compound, while zineb and ethylene thiourea were detected only in all examined samples in group II which were identified and confirmed by TLC, HPLC and spectral analysis. Addition of Zingiber officinales Rosc [ginger 1%, w/w], on a diet containing zineb at a dose of 100 ppm, significantly ameliorate the toxic effect of zineb to a large extent. Also addition of ginger to contaminated diet with zineb led to decrease the levels of zineb and ethylene thiourea and to disappearance of the other metabolites Hence, the present findings will provide a potential scope for future use of ginger as chemopreventive agent against fungicides toxicity and emphasize the potential of natural plant products as chemopreventive agents

Serum endothelin-1 in obesity: the effect of weight reduction

Recent studies have shown that endothelin-1 [ET-1] is implicated in avariety of pathological conditions including obesity, diabetes mellitus, essential hypertension and astherosclerosis. The aim of the present work was to examine the relationship between ET-1 with some anthropometric and metabolic variables characteristic of insulin resistance syndrome The effects of energy restriction either alone or in combination with metformin on serum ET-1, some anthropometric and metabolic variables characteristic of insulin resistance syndrome were also studied. The study included 40 obese female patients with age ranging from 47 to 53 years. They were divided into two groups. Group I included 30 obese female patients with either IGT or newly diagnosed type 2 diabetes with insulin resistance syndrome, group II included 10 obese females without IRS and were taken as a control. Both groups were matched in age, and BML. Patients in group I was divided into two groups. Group I received LCD [1200 kcal/day] alone, Group 2 received low calorie diet plus metformin ,[850mg twice daily]. The study continued for 6 months. All patients were subjected to thorough history taking and clinical examination stressing on weight, height, BMI, WHR and blood pressure. Fasting 2 hour postprandial plasma glucose, HBAIc, HOMA-IR lipogram and ET-1 were also assessed. These parameters were also evaluated after dietary intervention and metformin treatment. From this study, we found that patients with IRS were obese, BMI [33.57 +/- 1.7] with significant increase in WHR compared to obese controls, Also there was significant increase in SBP, DBP, fasting postprandial plasma glucose, fasting insulin insulin, HOMA-IR, total cholesterol, LDL-C, TG and significant reduction in HDL-C in obese patients with IRS in comparison with obese controls. Also resum ET-1 were significantly increased in obese patients with IRS compared to controls. Also, there was significant correlations between serum ET-1 and some parameters present in IRS e.g. BMI, WHR, SBP, DI3P, fasting and postprandial plasma glucose, HbAlc, fasting insulin, HOMA-IR and lipid profile. The following results were obtained after dietary intervention and metformin treatment: Significant decrease in BMI, WHR, blood pressure, fasting, postprandial blood glucose, HbAlc, HOMA-IR, total cholesterol, LDL-c in both groups with more reduction in LCD+metformin group HDL-C also significantly increased in both groups with more significant increase in LCD+metformin group. ET-1 were significantly reduced in LCD metformin group. We can conclude that insulin resistance syndrome is a constellation of clinical and biochemical anomalies clustering in subjects with upper body fat distribution. ET-1 also may be involved in. the pathogenesis of many components of IRS e.g. insulin resistance, hypertension dyslipidaemia. Insulin ET-1 production and ET-1 decreased insulin sensitivity so, ET-1 may play another key underlying role in IRS through its close relation with insulin resistance. LCD and metformin are effective and safe measures in the management of obese patients with IRS as they improve many components of this syndrome. Their effects may be explained partly by their effect on insulin resistance and plasma ET-1

Subclinical hypothyrodism, is it mild thyroid failure to treat or acompansated state?

Subclinical hypothyroidism "SCH" affects of general 5-15% of general population, however the need of lifelong L-thyroxin "LT4" therapy is still controversial. As the serum lipids and myocardium are main targets of thyroid hormone action, we investigate whether SCH induces serum lipids and cardiovascular alterations and we evaluate the effect of L-T4 replacement therapy on clinical symptoms, serum lipids and echocardiographic parameters in patients with SCH. We studied 20 premenopausal women with subclinical hypothyroidism with age ranging from 18-45 years and 20 premenopausal euthyroid women as control group matched to SCH patients for age and body mass index [BMI]. Patients were randomly classified into two sub-group each included 10 women, one group received L-T4 therapy and the other group receive placebo for the same period. All were subjected to through clinical assessment, assessment of tissues hypothyroidism using zulewski Score, serum total cholesterol [TC] law density lipoprotein cholesterol "LDL-C", high density lipoprotein cholesterol "HDL-C" and triglycerides "TG" also echocardiography 2D, M-Mode and Doppler study. Our study revealed significant elevation of total cholesterol and LDL-C in SCH patients than control and after L-T4 therapy, there was significant improvement of both clinical score and serum lipids. Also SCH patients had significantly higher isovolumetric relaxation time "IVRT' and peak A value than control moreover preejection period "PEP" as well as PEP/ET were significantly longer in patients than controls and these changes fully reversed after L-T4 therapy. SCH patients has negative clinical metabolic and echocardiographic effects and these negative effects are fully reversible after LT4 therapy. Therefore subclinical hypothyroidism is better considered a condition of minimal tissues hypothyroidism than a compensated state. Indeed, L-T4 replacement therapy should be advised for these patients with the aim to prevent both the progression to frank hypothyroidism and the development of clinically significant myocardial dysfunction

Role of Omega-3 essential fatty acids in pregnancy induced hypertension

Pre-eclampsia is a major health problem contributig largely to maternal and neonatal morbidity and mortality which is of obscure etiology. It is characterized by vasoconstriction and platelet aggregation which is attributed to imbalance of thromboxane A2 and prostacyclin A2. This imbalance could be corrected by polyunsaturated fatty acids of n-3 class by competing with arachidonic acid for cyclooxygenase enzyme producing inactive prostanoid. To study the relation of omega-3 fatty acids and the severity of pre-eclampsia. 10 mild pre-eclamptic, 10 severe pre-eclamptic and 10 eclamptic patients were compared to a control group of 20 normal pregnant patients for their plasma levels of omega-3 fatty acids using high performance liquid chromatography. pre-eclamptic patients were significantly lower in their plasma levels of fatty acids than in control group

Effect of aging on the physico-chemical stability of acetazolamide and phylpropanolamine hydrochloride tablets

The effect of ageing on the physicochemical stability of acetazolamide and phenylpropanolamine HCl tablets, directly compressed with Dynasan 114 and 118, was studied. Three temperature levels [25, 40 and 60C] at 75% relative humidity were adopted, either in closed or open containers over a 6-month storage period. The results revealed that the tablets stored in closed containers did not exhibit any significant changes in properties. However, tablets containing Dynasan 114 and stored at 60C were completely deformed after 4 months. All tablets stored at 75% relative humidity showed a significant increase in their weights and decrease in hardness values. The disintegration time and dissolution profiles [t 50%] of acetazolamide tablets containing Dynasan 114 or 118 were not affected by phenylpropanolamine HCl tablets, containing Dynasan 114 or 118, caused a decrease in their disintegration times and t 50%. The drug content and uniformity of weight of both drug content and uniformity of weight of both tablets were not affected in all formulations under the tested storage conditions

Formulation and stability of atropine sulfate eye drops

Atropine sulfate was formulated in ophthalmic solutions using methylcellulose, sodium carboxymethylcellulose, polyvinyl alcohol, polyethylene glycol 6000, and polyvinyl-pyrrolidone K25. The formulations were subjected to stability studies. The obtained results revealed that, no degradation or complexion occur among the tested preparations with the exception of that contained methylcellulose. A significant decrease of drug content and viscosity of the solution was appeared after storage for the first month. Furthermore, the degradation in drug concentration was reached more than 60% after storage at 70C for two years. Also, TLC revealed a chemical decomposition of atropine sulfate in methylcellulose solution

Effect of atropine sulfate ointments and gels on the intraocular pressure of rabbit's eye

Atropine sulfate has been formulated in ointments and gels using absorption base, hydrocarbon base, water soluble base, polyvinylpyrrolidone gel and sodium carboxymethylcellulose gel. The release behaviour of the drug and the effect on intraocular pressure of rabbit's eye have been estimated. The results revealed that, the release of atropine sulfate was in the following order, polyvinylpyrrolidone gel > polyethylene glycol > sodium carboxymethylcellulose gel > lanolin-petrolatum > hydrocarbon base. However the maximum effect of drug on intraocular pressure was maintained within three hours in the following order, sodium carboxymethylcellulose gel < hydrocarbon base < polyethylene glycol base < polyvinylpyrrolidone gel < lanolin-petrolatum base

Effect of vehicle composition on bioavailability of atropine sulfate in rabbit's eyes

The effects of vehicle composition on ocular disposition of atropine sulfate was studied using different ophthalmic drops, ointments and gels on rabbit's eyes. The bioavailability of the drug in eye tissues showed that, their distribution were greatly affected by the type of the vehicle. In addition, the uptake by different eye tissues was variable. The peak time of atropine sulfate was found to be 2 hours for ophthalmic drops and 3 hours in case of ointments and gels. The total bioavailability of atropine sulfate in eye tissues of rabbit and aqueous humor after 2 hours were 4350,4010 and 3675 ugm/gm using NaCMC, PVP and PEG ophthalmic drops. While that from ointments and gels after 3 hours were 4355, 4320, 4255 and 4205 ugm/gm for PVP gel, PEG base, hydrocarbon base and NaCMC gel respectively

Cervical colonization with actinomyces in women using intrauterine contraceptive devices

Intrauterine contraceptive device [IUCD] was found to promote colonization by actinomyces species. The presence of cervical actinomyces colonization was verified by using direct endocervical smears stained by simple gram stain, it was found among 10% of long term IUCD users. By using culture on brain heart infusion blood agar containing 2.5 mg/L metronidazole, anaerobically incubated for a fortnight, the prevalence was 2% of long term IUCD users. The removed loops of these two cases were positive. Actinomyces was not detected among short term IUCD users. No statistical significant difference between negative, positive and control cases in age, parity and duration of marriage, however the frequency of sexual intercourse was an important which affected the colonization of the cervix with actinomyces species. Though most of the cases with positive actinomyces were asymptomatic, it seems wise enough to overcome this colonization by frequent change of IUCD and not allowing them to st and in utero for long periods

Formulation and release characteristics of phenylephrine hydrochloride suppositories

Phenylephrine hydrochloride suppositories were formulated using Witepsols H[15], W[35] and E[75] each alone or in combinations of two in different ratios of 1:1, 1:2 and 2:1. The prepared suppositories were evaluated for their mechanical properties, release characteristics and drug partitioning using different bases and water. The obtained results revealed that the prepared suppositories exhibited good mechanical properties and different release characteristics. The partition coefficient of the drug was found to be in a good correlation with its release profiles from the corresponding bases. Witepsol W[35] either alone or in combinations with E[75] or H[15] in a ratio of 2:1 [W[35]:E[75] or H[15]] were found to be the bases of choice for formulating phenylephrine hydrochloride suppositories referring to their good mechanical properties and high release characteristics. The bioavailability of the drug after rectal administration in rabbits was greater with Witepsol W[35] over Witepsols H[15] and H[15]+W[35] [1:2]. A highly significant in-vivo in-vitro correlation existed

Application of factorial design of experiments to predict the chemical stability of ferrous fumarate and thiamine hydrochloride tablets

In this-investigation factorial design of experiment of the type N = 2 [3]was applied to predict the chemical stability of ferrous fumarate and thiamine 'hydro chloride in tablets prepared by direct and wet granulation techniques, using Span 40, stearic acid and PEG 6000 as granulating agents. The quantitative factors were the temperature, humidity and time, corresponding to the accelerated storage conditions which are 52% and 95% relative humidity at two temperature levels [25 and 42 C]. The effect of the three operating factors and their interactions on the stability of both drugs as well as the derivation of impervical, regression equations were determined. The derived regression equations have the ability to predict the chemical stability of ferrous fumarate and thiamine hydrochloride tablets at any particular conditions within the limits specified. In addition, the coefficients of the factors and their interactions were found to have negative signs, which indicated that the effect of each factor was dependent on the level of the other two factors. The obtained results revealed that, there was very good agreement between the predicted and the experimental data obtained from the classical design of the experiments, carried out under the specified storage conditions. The reaction rate constants and [90%] of ferrous fumarate and thiamine hydrochloride tablets determined from the regression equations were found to be parallel with those determined from the first order plots. These findings indicated that, with the help of factorial design of experiments it could be possible to predict the expiry date of such tablets in a short time and less cost of experimentation

Release characteristics of saluzide from suppository bases

Saluzide suppositories were prepared using Witepsols and polyethylene glycols [PEG] bases. The physicochemical and the release behaviour of drug from the prepared suppositories were investigated. The data of release of drug were analyzed according to order of kinetics. It was found that the release of saluzide from Witepsols was lower than that from PEG. In addition the rate of release was found to be diffusion controlled from the fatty bases. However, the first order kinetic fitted the release of drug from suppositories prepared using PEG

Study on the effect of the combination of propranolol hydrochloride and pilocarpine hydrochloride on intraocular pressure of rabbit's eye

Pilocarpine hydrochloride and /or propranolol hydrochloride were formulated in aqueous solutions and gel form using methyl cellulose and sodium carboxymethylcellulose as thickening and gelling agents, respectively. Both formulations were instilled into normal rabbit's eyes and the changes in the intraocular pressure [IOP] were determined. It was found that the action of both drugs on the intraocular pressure was significantly increased in the presence of the added polymers. Moreover, the optimum decrease in IOP was reached in a shorter time with aqueous solution [2 h] and gel form [3 h] than with control drugs without polymer [4 h]. The peak heights of such decrease were in percentage for pilocarpine hydrochloride 7.2, 27.5 and 17.9, for propranolol hydrochloride 12.5, 18.4 and 17.3 and for their mixture 15.4, 15.4, 15.4 and 16 as aqueous solution, aqueous solution with methylcellulose and gel form, respectively. The study showed that the use of propranolol hydrochloride with pilocarpine hydrochloride with pilocarpine hydrochloride in a concentration of 1% each causes a maximal decrease in IOP in presence of methylcellulose as a thickening agent