Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology.

The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations. A standard screw configuration was applied, and the last zone of the barrel was opened to discharge water vapors, which helped to manufacture non-sticky, clear, and uniform films. The film formulations demonstrated rapid disintegration times (6-11s) and more than 95% dissolution in 5min. In addition, the films had characteristic mechanical properties that were helpful in handling and storage. An animal model was employed to determine the taste masking of melt-extruded films. The lead film formulation was subjected to a human panel for evaluation of extent of taste masking and disintegration.

A study on knowledge and awareness about tuberculosis in senior school children in Bangalore, India.

BACKGROUND: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), commonly affecting the lungs. All health care professionals including the pharmacists provide a valuable public health role in promoting community awareness of TB particularly in reducing stigma attached to TB. Thus, creating awareness at a community level could play a vital role in control and prevention of TB. OBJECTIVES: To determine whether educational intervention would affect the level of TB awareness among students of selected schools and pre-university colleges (PUCs) in Bangalore urban and Bangalore rural regions. METHODOLOGY: The present study was conducted among the students of 8th, 9th, 10th and PUC in Bangalore rural and urban jurisdiction (n=2635). A questionnaire was designed in English and Kannada language, consisting of 20 questions with multiple-choice answers. A 30-minute visual health education was given on TB in English, followed by general pictorial presentation, and the data were collected as pre-test and post-test. RESULTS: Data collected from 2635 participants during pre- and post-education session revealed that mean score improved from 8.77±2.59 to 14.95±1.99. Impact of the education session showed a significant knowledge improvement about TB from 1.59% (pre-education) to 49.67% (post-education). CONCLUSION: The present study clearly demonstrated that a simple, 30-minute health education session did have a positive impact on knowledge and awareness about TB among school children as observed with increase in mean knowledge score from pre-test to post-test, indicating that empowerment of students could guide the community on various aspects of TB.

Taste Masking of Griseofulvin and Caffeine Anhydrous Using Kleptose Linecaps DE17 by Hot Melt Extrusion.

The objective of this project was to investigate the potential of Kleptose Linecaps DE17 (KLD) in masking the unpleasant/bitter taste of therapeutic agents by hot melt extrusion (HME). Griseofulvin (GRI) and caffeine anhydrous (CA) were used as a bitter active pharmaceutical ingredient (API) model drugs. Thermogravimetric studies confirmed the stability of GRI, CA, and KLD at the employed extrusion temperatures. The differential scanning calorimetry (DSC) studies revealed a characteristic melting endotherm of GRI at 218-220°C and CA at 230-232°C in the physical mixtures as well as in all extrudates over the period of study, indicating the crystalline nature of drug. HME of KLD was achieved only in the presence of plasticizer. Among the several plasticizers investigated, xylitol showed improved processability of KLD at 15% w/w concentration. Dissolution studies of HME extrudates using simulated salivary medium exhibited ∼threefold less release compared to physical mixture at the end of 5 min (the lesser drug release, better the taste masking efficiency). Furthermore, the results from the sensory evaluation of products in human panel demonstrated strong bitter taste in the case of physical mixture compared to the HME formulation, suggesting the potential of Kleptose Linecaps DE17 as taste masking polymer in melt extruded form.

Development of taste masked caffeine citrate formulations utilizing hot melt extrusion technology and in vitro-in vivo evaluations.

The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release. A modified screw configuration was applied to improve the extrusion processability and to preserve the crystallinity of the API. The milled extrudates were subjected to dissolution testing in an artificial salivary fluid and investigations using e-tongue, to assess the extent of masking of bitter taste of the API. There was an insignificant amount of drug released from the formulation in the salivary medium while over 80% of drug released within 30 min in 0.1N HCl. ODTs were also developed with the extrudate mixed with mannitol and crospovidone. The quality properties such as friability and disintegration time of the ODTs met the USP specifications. The lead extrudate formulations and the ODTs prepared using this formulation were subjected to human gustatory evaluation. The formulations were found to mask the unpleasant taste of caffeine citrate significantly.

Liposomes as carriers of the lipid soluble antioxidant resveratrol: evaluation of amelioration of oxidative stress by additional antioxidant vitamin.

AIM: Resveratrol (RES) is a well-known antioxidant, yet in combination with other antioxidant vitamins, it was found to be more effective than any of these antioxidants alone. Present work aims to compare the antioxidant actions of resveratrol with and without vitamin C following delivery as liposomes tested using chemical and cellular antioxidative test systems. MAIN METHODS: Liposomes were prepared by the thin film hydration method and characterised for percent drug entrapment (PDE), Z-average mean size (nm), polydispersity index (PDI) and zeta potential. Antioxidative capacity was determined by studying the inhibition of AAPH induced luminol enhanced chemiluminescence and inhibition of ROS production in isolated blood leukocytes. Intracellular oxygen-derived radicals were measured using flow cytometry with buffy coats (BC) and human umbilical vein endothelial cells using H2DCF-DA dye. KEY FINDINGS: Particle size varied from 134.2 ± 0.265 nm to 103.3 ± 1.687 nm; PDI ≤ 0.3; zeta potential values were greater than -30 mV and PDE ≥ 80%. Radical scavenging effect was enhanced with liposomal systems; oxidative burst reaction in BC was inhibited by liposomal formulations, with the effect slightly enhanced in presence of vitamin C. Reduction in reactive oxygen species (ROS) production during spontaneous oxidative burst of BC and incubation of HUVECs with H2O2 further intensified the antioxidative effects of pure RES and liposomal formulations. SIGNIFICANCE: The present work clearly shows that the antioxidative effects of resveratrol loaded into liposomes are more pronounced when compared to pure resveratrol. Liposomal resveratrol is even active within the intracellular compartments as RES could effectively quench the intracellular accumulation of ROS.

Drug-drug interactions of anti-infective drugs: utility of fluorescence cyp inhibition assays in drug discovery.

Drug interactions are often a result of induction or inhibition of cytochrome P450 (CYP) enzymes by co-administered drugs. A high throughput fluorescence assay using cDNA-expressed human CYP isozymes and fluorogenic substrates has been reported for the study of CYP inhibition. We used this assay to evaluate CYP inhibition profiles of 21 marketed anti-infective drugs. We found that six of the eight potent inhibitors identified in this screen (IC50 <10 microM against at least one CYP isozyme) correlated with significant drug-drug interactions in the clinic. In contrast, the intermediate and weak inhibitors (IC50 >10 microM) did not indicate clinically significant drug interactions. Furthermore, we observed that results obtained in the fluorescence assay correlated with conventional, well-established, low throughput methods that utilize human liver microsomes. These data suggest that in the early stages of drug discovery, the fluorescence assay for CYP inhibition could be used in conjunction with a human liver microsomal assay to identify new chemical entities with a potential for drug-drug interactions.

Nuclear quadrupole resonance studies of transparent conducting oxides.

We report (63,65)Cu spin-lattice relaxation rates measured by nuclear quadrupole resonance (NQR) in the delafossite compound CuYO(2) and CuYO(2):Ca over a temperature range from 200 to 450K. CuYO(2):Ca is a prototype transparent oxide exhibiting p-type electrical conductivity. Relaxation rates in CuYO(2):Ca are enhanced by one to two orders of magnitude relative to undoped material, exhibit much stronger temperature dependence, and contain contributions from magnetic and quadrupolar relaxation mechanisms with roughly equal strengths. Relaxation in undoped CuYO(2) is of purely quadrupolar origin and is attributed to interactions with lattice phonons. The main focus of this paper is the magnetic contribution to the relaxation rate in CuYO(2):Ca which is attributed to the hyperfine fields of carriers. It is argued that the dynamics of the hyperfine field are dominated by the hopping rate for carrier transfers between neighboring atoms in the copper planes of the delafossite structure. Comparison of the magnetic relaxation rates with the DC conductivity permits an estimate of the carrier concentration and mobility.

Membrane sweeping in conjunction with labor induction.

OBJECTIVE: To determine whether cervical membrane sweeping (stripping) during induction of labor is beneficial. METHODS: We compared outcomes of labor after induction in pregnant women at term in a randomized trial. Women were assigned to having their membranes swept or not during induction. Outcome measures included duration of labor, maximum dose of oxytocin used, induction-labor interval, and mode of delivery. RESULTS: We recruited 130 nulliparas (64 sweep, 66 nonsweep) and 118 multiparas (60 sweep, 58 nonsweep). Among nulliparas who received intravaginal prostaglandin (PG) E(2) and oxytocin, those who had simultaneous sweeping had significantly shorter mean (+/- standard error of mean) induction-labor interval (13.6 +/- 1.4 versus 17.3 +/- 1.2 hours, P =.048), lower mean maximum dose of oxytocin (6.8 +/- 0.8 versus 10.35 +/- 1.1 mU/minute, P =.01), and increased normal delivery rates (vaginal delivery 83. 3% versus 58.2%, P =.01). Sweeping also had a favorable effect on nulliparas who received oxytocin alone (mean induction-labor interval 5.8 +/- 3.1 versus 11.2 +/- 3.6 hours, P =.04; mean maximum dose 8.8 +/- 1.3 versus 16.3 +/- 1.9 mU/min, P =.01). Those differences were limited to women with unfavorable cervices. There were no differences in any outcome measures in multiparous women. CONCLUSION: Sweeping of the membranes during induction of labor had a beneficial effect on labor and delivery, which appeared to be limited to nulliparas with unfavorable cervices who needed cervical priming with PGE(2).

Correlation of change in uterine activity to blood loss in the third stage of labour.

In 47 women, the change in the uterine activity after the administration of a uterotonic agent was correlated with the amount of blood loss during the same period of time. Uterine activity was measured by a Gaeltec catheter-tipped pressure transducer inserted transcervically within 5 min of delivery of the placenta. A uterotonic agent (either intravenous syntocinon, intramuscular syntometrine or oral misoprostol) was given after the insertion of the intrauterine pressure catheter and pressure recorded for another 90 min. Blood loss over the same 2-hour period was collected with absorbent paper which was then assessed by colorimetric measurement of the haemoglobin content in the sample. Our results show that the change in uterine activity is associated with the total blood loss. However, there is a poor linear correlation between the two variables probably because of the biological variation in myometrial activity and differences in coagulation mechanisms in normal women.

Validation of a laboratory method of measuring postpartum blood loss.

Laboratory methods give more accurate measurement of blood loss in the postpartum period than visual estimation. In order to evaluate a laboratory method used to quantify blood loss postpartum, blood lost at gynecological operations was collected in a measuring bottle. The measured amount of blood (50-1,000 ml) was then poured onto absorbent paper towels and sanitary pads, in order to mimic conditions when measuring blood loss in clinical trials in the postpartum period. The amount of blood absorbed onto the absorbent paper and sanitary pads was measured by a rapid method of automatic extraction and photometric measurement of alkaline hematin. The study shows that the method provides a reliable and accurate means of measuring blood loss. The error in each case was less than 10% with an intraclass correlation coefficient of almost 1.

The reliability of catheter-tip transducers for the measurement of intrauterine pressure in the third stage of labour.

In order to assess the reliability of intrauterine pressure measurements in the third stage of labour, catheter-tip transducers were used in 20 women randomly allocated into two groups of 10. In each case in the first group two catheters were tied together and introduced transcervically into the uterine cavity after delivery of the placenta. In each case in the second group two catheters were inserted independently into the same uterine cavity. The active and cumulative active pressures recorded from the pairs of catheters within each uterine cavity were compared. Comparison of individual active pressure readings from separate transducers revealed good agreement whether the catheters were tied together or were separate. Cumulative active pressure was very similar when assessed by each catheter in the same uterus. Intrauterine catheter-tip transducers can be used reliably to measure uterine activity in the third stage of labour although there may be minor contraction by contraction differences in recordings of individual active pressures.

Preinduction cervical ripening: prostaglandin E2 gel vs hygroscopic mechanical dilator.

OBJECTIVES: To evaluate the efficacy and safety of hygroscopic mechanical dilators (Dilapan) for ripening the pregnant cervix prior to induction of labour at or near term and to compare it with an intracervical PGE2 gel (Prepidil). METHODS: One hundred and eighty-five women (69 nulliparae, 116 multiparae) at term with singleton pregnancies in cephalic presentation, who were scheduled for induction of labour in the labour ward at the National University Hospital, but had an unfavourable cervical score were randomized into 2 groups by random number table. In group 1 (Prepidil), 0.5 mg of PGE2 in 2.5 ml of triacetin gel was inserted into the endocervical canal. In women in group 2 (Dilapan) upto a maximum of 4 hygroscopic dilators were placed in the endocervical canal. If labour did not ensue at the end of 12 hours of ripening, the cervical score was assessed, amniotomy was performed and oxytocin commenced. Neonatal and obstetric outcome was compared, statistical analysis performed using Chi-square, and t-tests. RESULTS: Significantly more women in the group who received Dilapan for cervical ripening required amniotomy and oxytocin for induction of labour > 12 hours after priming compared with the group who received Prepidil (p < 0.001). Operative delivery for no progress and fetal distress respectively was similar in the 2 groups. The number of cases of hyperstimulation were higher in the Prepidil group but did not result in an increased incidence of operative deliveries for fetal distress. There was one neonatal death and one case of neonatal sepsis in the Dilapan group. Uterine rupture occurred in 1 woman who received Prepidil. CONCLUSION: Dilapan, a mechanical method of cervical ripening is as effective as the more widely accepted mode of ripening with an endocervical PGE2 gel in achieving vaginal delivery. Dilapan would be useful for cervical priming prior to induction of labour in places where prostaglandins are not available because of cost and the need for a cold chain.

The role of transvaginal ultrasonography and colour Doppler imaging in the detection of ectopic pregnancy.

OBJECTIVE: To assess the use of transvaginal ultrasound and colour Doppler imaging in the detection of ectopic pregnancy. MATERIALS AND METHODS: Seventy-one patients with suspected ectopic pregnancies had transvaginal sonography and colour Doppler imaging performed and 61 ectopic pregnancies were confirmed at surgery. Various ultrasound features on transvaginal B mode scanning were noted and the resistance index of peritrophoblastic flow in the adnexal masses computed. RESULTS: The use of transvaginal B mode imaging alone in the diagnosis of ectopic pregnancy achieved a sensitivity of 98% and a positive predictive value of 86%. The mean gestational age at time of diagnosis was 6 weeks 5 days (range 4 weeks to 13 weeks 2 days). The use of transvaginal colour flow imaging did not increase detection rates of ectopic pregnancy. The mean RI values for patients with or without ectopic pregnancy were almost identical. CONCLUSION: Colour Doppler imaging failed to improve on the results of transvaginal B mode sonography in the detection of ectopic pregnancy.

Breast feeding pattern in urban infants in Chandigarh.

PIP: The pattern of breastfeeding and the factors which determine the practice were assessed in 670 mothers from urban areas of Chandigarh. Unsupplemented breastmilk was administered to only 36.6% of babies up until 4 months of age. Women from the lower socioeconomic class, uneducated, and poorly educated mothers were more successful than those from the upper socioeconomic clases or those with higher education (P0.01). The success rate for breastfeeding was higher among babies born at home (50.0%) as compared to those born in the hospital (32.3%). Similarly, high proportions of male infants were successfully breastfed (40.3%) as compared to females (31.6%). Among those infants weaned breastfeeding was discontinued before 1 month of age in more than 60%. The main reason that breastfeeding failed was insufficient milk. Promotional efforts for unsupplemented breastfeeding should consider some of the above factors for their success.^ieng

Beliefs and practices of urban mothers regarding "hot" and "cold" foods in childhood illnesses.

Beliefs and practices of 100 urban mothers regarding "hot" and "cold" foods during four common childhood illnesses were determined by using a pretested, partly structured interview schedule. Egg, by 60% of mothers, mango by 52%, lentils by 49%, jaggery by 46% were considered "hot" properties. "Hot" foods were preferred and "cold" foods restricted in the treatment of cough and cold and illnesses with rash. In diarrhoea, "cold" foods were preferred and "hot" foods restricted. The knowledge that many food combinations and certain procedures are believed to change the properties of common food may be utilized in promoting the consumption of nutritionally balanced diets. Introduction of culturally acceptable education in nutrition which incorporates the above knowledge is likely to help in the prevention of protein-energy malnutrition and to increase parental co-operation during therapy.