Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

Formulation and evaluation of orally disintegrating clopidogrel tablets

ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs) that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC). DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.

RESUMO Recentes avanC'os em sistemas de liberaC'C#o de fC!rmacos novos visam C obtenC'C#o de melhor adesC#o do paciente. Um destes avanC'os C) a formulaC'C#o de comprimidos de desintegraC'C#o oral (ODTs), que se dissolvem instantaneamente, liberando o fC!rmaco, em alguns segundos, sem a necessidade de C!gua. O principal objetivo deste trabalho foi preparar e desenvolver ODTs de clopidogrel. Os ODTs foram preparados pelo mC)todo de compressC#o direta. Estudou-se o efeito de vC!rias concentraC'C5es de diferentes agentes de desintegraC'C#o, tais como super-crospovidona, croscarmelose de sC3dio, glicolato de amido de sC3dio no tempo de desintegraC'C#o e velocidade de dissoluC'C#o. Os comprimidos preparados foram avaliados quanto C dureza, C friabilidade, ao tempo de desintegraC'C#o e C liberaC'C#o do fC!rmaco in vitro. AlC)m disso, estudou-se a interaC'C#o de clopidogrel com os excipientes de formulaC'C#o, utilizando calorimetria de varredura diferencial (DSC). Estudos de DSC revelaram nC#o haver interaC'C#o entre o fC!rmaco e os excipientes utilizados. Todos os comprimidos possuC-am dureza na faixa de 4,0-5,2 kp e a friabilidade inferior a 1%. A variaC'C#o de peso e o teor de fC!rmaco de todas as formulaC'C5es mostraram-se dentro do limite oficial, de acordo com a BP. O estudo de liberaC'C#o do fC!rmaco in vitro de comprimidos ODTs mostrou que mais de 90% do fC!rmaco foram liberados em10 minutos. O teste de palatabilidade em voluntC!rios humanos mostrou sabor e sensaC'C#o na boca aceitC!veis. Assim, os resultados obtidos demonstraram, conclusivamente, a rC!pida e bem-sucedida desintegraC'C#o dos comprimidos formulados e a palatabilidade aceitC!vel.

Predicative factors for pegylated interferon-alpha plus ribavirin combination therapy in Egyptian patients with chronic hepatitis cinfected with genotype 4

Hepatitis C virus genotype 4 is a common infection in Egypt and is the leading cause of liver disease. Most reports suggest that predicative factors for the efficacy of interferon alpha and ribavirin combination therapy for chronic hepatitis patients could be due to the mutations in the interferon sensitivity determining region. The present study aimed to investigate the predictive factors for combined pegylated interferon-alpha and ribavirin therapy for chronic hepatitis patients with HCV genotype 4. The study was carried out on forty patients with genotype 4 chronic hepatitis C receiving a weekly dose of 180 microg of PEG -IFN-alpha in combination with RBV for 48 weeks. HCV RNA serumviremia levels were determined by a real-time polymerase chain reaction. The RNA samples were genotyped using specific primers for HCV genotype 4, and the interferon sensitivity determining region was amplified using polymerase chain reaction and sequenced. The amino acid sequence of the ISDR was compared with the published sequence for HCV 4 [GenBank: ABD75831.1]. Our data revealed that twenty one patients were responders [R; 52.2%], whereas 19 patients showed no-response [NR; 47.5%] to the combined pegylated interferon-alpha plus ribavirin therapy. The values of RNA titer in both responder and non-responder groups were statistically significant and could be used a predictive factor for combined pegylated interferon -alpha plus ribavirin efficacy. Other factors, such as gender, age, and interferon sensitivity determining region subtype were not related to its efficacy. These data collectively suggest that HCV RNA titer is an important factor for predicting the efficacy of pegylated interferon alpha plus ribavirin combination therapy in Egyptian patients with chronic HCV genotype 4

Perioperative acute phase response and outcome of hepatic resection, an experimental study

Identification of patients at risk of postoperative complications could have an impact on the indications for a procedure as well as permitting modifications of treatment to reduce the surgical risk. This experimental study evaluated the correlation between peri-operative acute phase response and outcome of hepatic resection. The study was conducted on sixty healthy golden hamsters, which underwent partial hepatectomy. They were arranged in 3 groups [20 per each]. One day prior to resection, fracture of the left hind leg was done in group I [GI] and wound infection had been created in group II [GII]; while nothing done in group III [GIII] that acted as a control. Blood samples to estimate SGPT and serum albumin [as basic investigations for hamsters liver function] and serum IL-6 and CRP [as acute phase reactants] were taken preoperatively, immediately after resection and for the consecutive 3 days post operatively. The mean serum level of both acute phase reactants increased in GI and GII preoperatively and continues to rise immediately after resection. Post-operatively; among the three groups, the mean serum level of both reactants was higher in GI than in GII that was in turn higher than in GIII except when the postoperative complications were more severe than the other group, then this relation changed

association between elevated serum free fatty acids in the third trimester of pregnancy and preterm delivery

Preterm delivery is not only an important cause of neonatal morbidity and mortality, but also its long term effect causes severe problems for the off spring and for the mother. We conducted a case control study to evaluate the association between elevated serum total free fatty acids [FFAs] in the third trimester of pregnancy and the incidence of preterm delivery. Twenty preterm [gestational age 28-34 weeks] and 20 control women [gestational age>37 weeks] registered to El Shatby Maternity University Hospital were evaluated. Preterm delivery was based on ultrasonographic assessment of cervical length less than 2.5 cm and cervical dilatation>10mm in primigravida and 20-30 mm in multigravida. Evaluation of serum fasting FFAs in the third trimester was done for cases of preterm delivery and their matched controls of term delivery. Also, pregnancy complications of foetal birth weight and incidence of admission to neonatal intensive care unit were assessed. Data were gathered from women who delivered in addition to their caring obstetricians involved as well as reviewing their medical records. The mean level of FFAs was significantly elevated in preterm cases compared to term control [442.3 +/- 51.47, 315.15 +/- 69.14 respectively, P=0.001]. Women with high levels of serum FFAs had more than two folds increased risk for preterm delivery OR [2.5], 95% [CI] 1.2-2.4, p<0.001. Also, high FFAs levels were associated with increased incidence of neonatal admission to Neonatal Intensive Care Unit. This study suggests that elevated total serum FFAs during the third trimester of pregnancy might be a predisposing factor for preterm delivery in non obese uncomplicated pregnant women. Also, these changes of maternal lipid metabolism may influence FFAs delivery to the foetus that can affect foetal growth

Immunomodulatory therapy in chronic hepatitis C infection

The imbalance of Th1 and Th2 cytokine production may play an important role in immunopathogenesis of persistent HCV infection and disease progression. BCG vaccine induces TNF gamma, causing Th1 type immune response. This study aimed to demonstrate the immunomodulatory effect of BCG vaccine on the progression of Hepatitis C viral infection. Forty patients with chronic hepatitis C were included [Group I] as well as 10 healthy controls [Group II]. All participants were subjected to: clinical examination, laboratory investigations, HCV antibodies by ELISA, quantitative PCR for HCV, HBsAg, HBcAb, serum IL-4, serum IL-2, tuberculin test and BCG vaccine [patients only]. Tuberculin positive, diabetic and bilharzial patients were excluded. The previous work-up was repeated only to group I at 12 weeks after BCG vaccine. Showed significant statistical elevation of both IL-2 and IL-4 pre vaccination compared to controls. Significant statistical elevation in levels of IL-2 and lowering in levels of IL-4 at 12 weeks post vaccination occured in patients. Levels of IL-4 were still significantly higher than those of controls. A significant lowering of viremia as detected by quantitative PCR also occurred BCG vaccine could be considered a new line of immune therapy based on its immunomodulatory action on chronic hepatitis C patients

Gastrointestinal stromal tumors [GISTS]: clinical presentation, diagnosis, surgical treatment and its outcome

This study included 13 selected patients treated by surgical excision for lesions that proved postoperatively to be gastrointestinal stromal tumors [GISTs] by histopathological and immunohistochemistry studies. The demographic, clinical and operative reports data were collected. Eight cases were gastric GISTs, four cases were small bowel GISTs [jejunum 1 and ileum, 3] and GIST of the sigmoid colon was in one patient. Eight cases presented at the emergency department due to hematemesis [3], gastrointestinal obstruction [3], bowel perforation [1] and severe bleeding per rectum [1]. Three cases presented with a feeling of abdominal fullness and ill-defined palpable abdominal mass. Two cases were discovered incidentally during GIT endoscopy for dyspepsia. Diagnosis of GISTs was presumed on clinical basis and operative findings from gross morphological features. Complete resection [RO] was achieved for 12 tumors [92.3%]. The immunohistochemistry profile was positive for C-kit for all cases. One operative death was due to massive pulmonary embolism. Postoperative complications occurred in three [23%] as upper GIT bleeding [1], biliary gastritis [1] and wound infection [1], and one [7.69%] of ileum tumor recurrence

Denver peritoneovenous shunt in the management of refractory ascites due to chronic liver diseases: impact of patients selection on its outcome

Forty four patients with refractory ascites due to chronic liver diseases that fulfilling the inclusion criteria of selection were divided into 2 groups. The first group [G1, n=24] was subdivided into 2 subgroups according to degree of liver condition; GIa [n=11] with Child-Pugh class B and GIb [n=13] with early class C. The patients were subjected to P-V shunt [Denver group]. Similarly, patients in the second group [GII, n=20] were divided into 2 subgroups GIIa [n=10] and GIIb [n=10] respectively and treated by the repeated tapping and albumin infusion [control group]. Postoperative results revealed a significant increase in urine output [P

Screening of window HBV infection among Egyptian blood donors

Transfusion-transmitted viral infection is present worldwide among blood donors. In the present study prevalence of early acute HBV infection among the eligible blood units for donation was investigated. Sera [760] from Egyptian blood donors [636 [83.68%] males and 124 [16.32%] females], who met donor selection criteria, were routinely screened for HBsAg, HCV-Ab, HIV 1/2-Ab and Syphilis-Ab. Accepted blood units for donation were further tested for liver and kidney functions and the presence of HBc-IgM and HBV-DNA. Screening resulted in 38 [5%] HCV-Ab positive units, 9 [1.18%] HBsAg positive units and one [0.13%] Syphilis-Ab positive unit. Testing of the accepted units for donation [712, 597 [83.84%] male and 115 [16.16%] female] resulted in one [0.13%] HBc-IgM positive unit and 2/30 HBV-DNA positive units. The routine screening of blood unit, to some extent, discovered the current viral infection but failed to detect early acute or window HBV infections where HBsAg is absent. ALT and AST levels were not indicative in viral infection in accepted blood donors at window period. Our study suggests that sensitive methods for detection of HBV [e.g. PCR] may be recommended in screening of donated blood. Anti-HBc antibody should be tested routinely on all donated blood units

Conservative versus radical surgery for treatment of uncomplicated hepatic hydatid cysts

This work evaluated both radical and conservative surgical approaches in the management of hepatic hydatid cyst. A total of 32 cases with uncomplicated hepatic hydatid cysts were divided into 2 groups according to the type of surgery. Patients in the first group [n=18] were subjected to conservative surgery in the form of endocystectomy, omentoplasty with or without drainage. Cases in the second group [n= 14] underwent radical surgery that included closed pericystectomy, open pericystectomy, wedge hepatic resection or segmentectomy. The results showed that the use of rib cage retractor could avoid the need for thoracotomy incision with its morbidity to manage cysts at the dome of the liver. The mean operating time in GI [140.15 +/- 38.30 mm] was significantly shorter than in GII [190.4 +/- 50.2 mm], with P<0.05. The need of blood transfusion in GI [16.7%] was lesser than in GII [35.7%], but the difference was statistically not significant. The postoperative pain, evaluated by the number of IM analgesic injection was significantly lower in GI [7.2 +/- 3.3] than in GII [9.9 +/- 3.9] with P<0.05. Wound complications were more observed in GII. There was only one reported recurrence in G I in a case with multiorgan cysts that did not receive perioperative anthelmintic chemotherapy. So, conservative surgical management of uncomplicated hepatic hydatid cysts with perioperative anthelmintic chemotherapy supposed to be a simple, safe and effective approach. Its efficacy is comparable to radical surgical procedures with much less morbidity

New approach in surgical management of complicated umbilical hernia in the cirrhotic patient with ascites

A total of 23 consecutive patients operated upon on emergency basis for the treatment of complicated umbilical hernias associated with liver cirrhosis and ascites. The hernia was complicated by strangulation in 11 and ascitic fluid leak in twelve of the patients. Patients were assigned randomly in two groups. In the first group [GI, n = 12] peritoneal drainage at the conclusion of their surgery was done but no drainage was applied in the second group [Gil, n=12]. All patients were operated upon and when closed system peritoneal drainage was done, it was brought to outside of the abdomen through a separate stab. No negative pressure was applied. The main outcome measures were postoperative wound healing, control of ascites, complications, and hernia recurrence rate at follow up. The male/female ratio, Child's class, ascites severity, and mode of hernia complication were almost matched in both groups. Postoperative wound dehiscence occurred in four patients in G II [23.5%] but in none of GI. Control of ascites was achieved in all patients of GI. The overall mean hospital stay was significantly lower in-patient of GI than those of the G II [P < 0.0 1]. Recurrences of the hernia occurred in one patient only of the G I and in three of the G II on a mean follow- up of 19 +/- 3 months. So, postoperative closed peritoneal drainage in the management of complicated umbilical hernias associated with liver cirrhosis and ascites safe and effective in assuring postoperative wound healing, control of ascites and the prevention of hernia recurrence. It is specifically indicated in cases with bowel resection anastomosis and in patients with low preoperative serum albumin and history of rapid ascites re-accumulation under medical therapy

Role of coenzyme Q10 as adjuvant to statins in treatment of atherosclerosis

Tatins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase constitute the most powerful class of hypolipidemic drugs currently available .Several large clinical trials have shown that these drugs reduce major cardiovascular events by 20-30%. The objective of the current study is to demonstrate the effect of concomitant use of coenzyme Q10 and Lovastatin in treatment of atherosclerosis as a trial to augment the antiatherogenic effect of Lovastatin and to decrease its undesirable effects. Five groups of adult male rabbits were included, an untreated control group, hypercholesterolemic group,hypercholesterolemic group treated with Lovastatin [2 mg /kg/ day], hypercholesterolemic group treated with Co Q10 [3 mg / kg per day] and hypercholesterolemic group treated with both Lovastatin and Co Q10 for 6 weeks .At the end of experiment, serum level of total cholesterol [TC], low density lipoprotein cholesterol [LDL-C], high density lipoprotein cholesterol [HDL-C], triglycerides [TG], alanine aminotransferase [ALT], aspartate aminotransferase [AST] and creatine kinase [CK] were estimated. Histopathological evaluation of tissue sections from liver was also performed. Each of Co Q10, Lovastatin and combination of both produced improvement in serum lipids, Co Q10 decreased the hypercholesterolemia induced elevation of serum transaminases while combination of Co Q10 with Lovastatin augmented the antiatherogenic effect of Lovastatin and decreased both Lovastatin induced increase in serum transaminases and Lovastatin induced increase in serum creatine kinase. In conclusion, Co Q10 administration augment the hypolipidemic and antiatherogenic effects of Lovastatin and improve its important side effects such as myopathy and elevation of serum transaminases

Alcohol or traditional methods versus natural drying for newborn's cord care

This is a quasi-experimental study that aimed to compare the use of alcohol and traditional methods for newborn's cord care with a no-treatment approach, natural drying. The study also aimed to identify the factors associated with the occurrence of cord infection and time of cord separation. A convenient sample of 70 women with vaginal delivery, full-term and healthy babies was selected from postpartum departments of two university hospitals in Alexandria and Minia. A specially designed interview schedule was developed and utilized to collect data. Swabs were taken from the newborns' umbilical stumps on zero and 3rd day of birth to detect bacterial colonization. Follow-up was carried-out at home to assess methods used for cord care, babies' hygiene, cord infection and time of cord separation. The study revealed that traditional methods of cord care were used by women with higher mean age [30.8 +/- 7.8 years], from Minia [100%] or rural areas [71.4%], while alcohol and natural drying were used by women with lower mean age [27.7 +/- 4.8 and 24.8 +/- 6.5 years] respectively, from Alexandria [76% and 100%] respectively or urban areas [56% and 64.7%] respectively. Alcohol was used for male babies [76%], while traditional methods and natural drying were used for female babies [71.4% and 64.7%] respectively. Incidence of cord infection was Significantly lower among natural drying group [35.3%], and no Signs of systemic infection were observed among them. Rate of increase of bacterial colonization [from 0-3rd day of birth] was significantly higher in alcohol group [44%]. It was relatively similar with presence or absence of cord infection [33.3 and 32.1] respectively. Mean time of cord separation was longer among alcohol group [6.4 +/- 2.4 days], as compared with natural drying group [4.7 +/- 1.9 days] and traditional methods group [3.4 +/- 0.7 days]. Bathing baby while cord was attached was carried out by all women of alcohol and natural drying groups, Compared to only 28.6% of traditional methods group. Breast-feeding was significantly related to less incidence of cord infection [P= 0.008] and shorter time of cord separation [P= 0.002]. Incidence of cord infection was significantly related to using cloth diaper [P= 0.015], Using dry method for skin care [X2[2]=7.2917], giving tub bath [X2[1]= 4.1788] and delaying the bath to the 7th day of birth [P= 0.050]. Time of cord separation was significantly shorter with closed cord dressing [X2[2]=20.4028], in Minia, during spring, among male babies [X2[2]=15.0352], and in rural areas [X2[2]= 9.7608]. It was significantly longer with bathing the baby while cord was attached [X2[2]=27.9354], giving 2-3 baths/week or delaying the bath to the 7th day of birth [P= 0.049] and with Using cloth diaper [P= 0.0467]. So, moving from an intervention to a non- intervention, particularly in a healthy Population should be applied to the healthy naturalistic approach to care advocated in nursing. Also, only through Continuing efforts done to examine our assumptions about historic health Care routines, will we be able to demonstrate evidence based practice and to advance nursing care

Erectile dysfunction in chronic renal failure patients undergoing haemodialysis

In this study, 75 patients were subjected to clinical and laboratory investigations. Age, presence of hypertension, smoking history of ischemic heart disease and duration of dialysis were detected. Hemoglobin level, creatinine level, blood urea, albumin and glucose were evaluated. A control group of 148 healthy males, representing the general Egyptian population, was also included in the study. In view of the observed high prevalence of erectile dysfunction [ED] among hemodialysis [HD] patients, it was suggested that a complete health evaluation of male HD patients should include a discussion about erectile function in the standard clinical care program of patients with renal disease