Chemometric Models for Quantification of Carbamazepine Anhydrous and Dihydrate Forms in the Formulation

Carbamazepine (CBZ) exists in anhydrous and dihydrate forms. These forms differ in their solubility, dissolution rate, and subsequently in their oral bioavailability. The objective of this study is to develop multivariate chemometric models for estimation of the low level of carbamazepine dihydrate (CBZ-DH) in the CBZ formulations containing excipients of the commercial formulation. The selected excipients were mixed in proportions to make sample matrices ranging from 0% to 50% CBZ-DH. Fourier transform infrared (FTIR), near infrared (NIR), and hyperspectral imaging data were mathematically pretreated before the development of partial least square and principal component analysis regression models. The developed partial least squares regression and principal component analysis models demonstrated predictability of CBZ and CBZ-DH by multiple scattering correction and standard normal variate processing methods. Among the spectroscopic techniques used the model performance parameters such as root-mean-square error, standard error, and bias were found to be low for NIR compared to FTIR. The treated data have shown better model fitting than without treatment, which was demonstrated by correlation coefficient of 0.9778, 0.9824, and 0.9852 for FTIR, NIR, and hyperspectral imaging, respectively. Furthermore, the predicted values were found to be very close to the selected low level of independent samples having 5% CBZ-DH in tablet formulation.     

Estimation of Cardiac Depressant Activity of Ten Medicinal Plant Extracts from Pakistan

Ten medicinal plants extracts were pharmacologically screened for their cardiac activity on isolated rabbit heart, and showed significant negative inotropic activity with negative chronotropic effects. In all cases alcohol dried extracts were used and reconstituted in either water or ethyl acetate for these tests. The plant extracts which produced cardiac depression were Cactus grandiflora , Carissa carandas Linn., Duranta repens Linn., Eclipta prostrata Roxb., Heliotropium ophioglossum , Prosopis glandulosa , Scheweinfurthia sphaerocarpa A. Br., Solanum surattense Burm. f., Tephrosia uniflora Pers., Nardostachys jatamansi Dc. (Syn. Valeriana jatamansi ).     

Review of policies,data, and interventions to improve maternal nutrition in Afghanistan

Malnutrition contributes to direct and indirect causes of maternal mortality, which is particularly high in Afghanistan. Women's nutritional status before, during, and after pregnancy affects their own well‐being and mortality risk and their children's health outcomes. Though maternal nutrition interventions have documented positive impact on select child health outcomes, there are limited data regarding the effects of maternal nutrition interventions on maternal health outcomes globally. This scoping review maps policies, data, and interventions aiming to address poor maternal nutrition outcomes in Afghanistan. We used broad search categories and approaches including database and website searches, hand searches of reference lists from relevant articles, policy and programme document requests, and key informant interviews. Inclusion and exclusion criteria were developed by type of source document, such as studies with measures related to maternal nutrition, relevant policies and strategies, and programmatic research or evaluation by a third party with explicit interventions targeting maternal nutrition. We abstracted documents systematically, summarized content, and synthesized data. We included 20 policies and strategies, 29 data reports, and nine intervention evaluations. The availability of maternal nutrition intervention data and the inclusion of nutrition indicators, such as minimum dietary diversity, have increased substantially since 2013, yet few nutrition evaluations and population surveys include maternal outcomes as primary or even secondary outcomes. There is little evidence on the effectiveness of interventions that target maternal nutrition in Afghanistan. Policies and strategies more recently have shifted towards multisectoral efforts and specifically target nutrition needs of adolescent girls and women of reproductive age. This scoping review presents evidence from more than 10 years of efforts to improve the maternal nutrition status of Afghan women. We recommend a combination of investments in measuring maternal nutrition indicators and improving maternal nutrition knowledge and behaviours.     

Absorption enhancers in pulmonary protein delivery.

Extensive research efforts have been directed towards the systemic administration of therapeutic proteins and poorly absorbed macromolecules via various nontraditional, injection-free administration sites such as the lung. As a portal for noninvasive delivery, pulmonary administration possesses several attractive features including a large surface area for drug absorption. Nevertheless, achieving substantial bioavailability of proteins and macromolecules by this route has remained a challenge, chiefly due to poor absorption across the epithelium. The lungs are relatively impermeable to most drugs when formulated without an absorption enhancer/promoter. In an attempt to circumvent this problem, many novel absorption promoters have been tested for enhancing the systemic availability of drugs from the lungs. Various protease inhibitors, surfactants, lipids, polymers and agents from other classes have been tested for their efficacy in improving the systemic availability of protein and macromolecular drugs after pulmonary administration. The purpose of this article is to provide the reader with a summary of recent advances made in the field of pulmonary protein delivery utilizing absorption enhancers. This report reviews the various agents used to increase the bioavailability of these drugs from the lungs, their mechanisms of action and effectiveness, and their potential for toxicity.     

Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields

The use of stents for vascular disease has resulted in a paradigm shift with significant improvement in therapeutic outcomes. Polymer-coated drug-eluting stents (DES) have also significantly reduced the incidence of reobstruction post stenting, a disorder termed in-stent restenosis. However, the current DESs lack the capacity for adjustment of the drug dose and release kinetics to the disease status of the treated vessel. We hypothesized that these limitations can be addressed by a strategy combining magnetic targeting via a uniform field-induced magnetization effect and a biocompatible magnetic nanoparticle (MNP) formulation designed for efficient entrapment and delivery of paclitaxel (PTX). Magnetic treatment of cultured arterial smooth muscle cells with PTX-loaded MNPs caused significant cell growth inhibition, which was not observed under nonmagnetic conditions. In agreement with the results of mathematical modeling, significantly higher localization rates of locally delivered MNPs to stented arteries were achieved with uniform-field–controlled targeting compared to nonmagnetic controls in the rat carotid stenting model. The arterial tissue levels of stent-targeted MNPs remained 4- to 10-fold higher in magnetically treated animals vs. control over 5 days post delivery. The enhanced retention of MNPs at target sites due to the uniform field-induced magnetization effect resulted in a significant inhibition of in-stent restenosis with a relatively low dose of MNP-encapsulated PTX (7.5 μg PTX/stent). Thus, this study demonstrates the feasibility of site-specific drug delivery to implanted magnetizable stents by uniform field-controlled targeting of MNPs with efficacy for in-stent restenosis.     

Contraindications and side effects of commonly used medications in coronary CT angiography

For certain clinical applications, coronary CT angiography (CCTA) has become a useful tool for the noninvasive evaluation of coronary artery atherosclerosis. To optimize image quality in CCTA, medications are often given prior to scanning to slow the heart rate or distend the arteries. These medications have side effects and are contraindicated in certain patient populations. Metoprolol is the ß-blocker of choice in CCTA, and it has been shown to be effective in achieving the goal heart rate of less than 65 beats per minute for CCTA and in minimizing variability of heart rate. It is contraindicated in patients with hypotension or high degree AV block, and it must be used with caution in patients with asthma or obstructive pulmonary disease, patients with decompensated heart failure, and those with vasospastic or vasoocclusive disease. Diltiazem, the calcium channel blocker of choice in CCTA, is a reasonable alternative for heart control, particularly in patients with asthma or bronchospastic disease, and patients with orthotopic heart transplants that have been sympathetically denervated. Sublingual nitroglycerin is especially useful in order to dilate distal arteries to improve stenosis visibility. However, it is contraindicated in patients on erectile dysfunction medications and those with severe anemia. It must be used cautiously in patients with aortic stenosis or other preload-dependant cardiac pathologies.     

Optimization and In Vivo Evaluation of an Oral Dual Controlled-Release Tablet Dosage Form of Insulin and Duck Ovomucoid

The objectives of the present study were to (1) optimize the release rate of insulin from compressed microparticulates and (2) compare the in vivo hypoglycemic effect of optimized insulin microparticulates with compressed enzyme inhibitor (duck ovomucoid) and without inhibitor. A 3-factor, 15-run Box Behnken design was used to construct polynomial models correlating the dependent and independent variables. Independent processing variables were rate of addition of the alcoholic Eudragit© L100 dispersion, volume of the antisolvent, and compression pressure. Responses were cumulative percent of insulin released from 1–6 hours. Insulin and ovomucoid release was simultaneously analyzed by high-performance liquid chromatography. They demonstrated variable release rates, which were optimized to the Higuchi's square root of time model to release the insulin and the inhibitor over 6 hours. The relationship between dissolution profiles and process parameters were demonstrated by contour and response surface plots. In vivo hypoglycemic effect was evaluated in rabbits in a 3-way crossover design. Cocompressed microparticulates of insulin and duck ovomucoid displayed a 3.2-fold greater hypoglycemic effect when compared with a similar preparation without ovomucoid. This study demonstrated the potential benefits of dosage forms with dual controlled-release mechanisms for both the protein and enzyme inhibitor.     

Cyp1b1 protein in the mouse eye during development: an immunohistochemical study.

We show, for the first time, the spatiotemporal appearance of Cyp1b1 protein during mouse eye ontogeny. The protein was unambiguously identified in the adult mouse eye and newborn (P0) whole mouse microsomes and was shown to be localized in inner ciliary epithelium, corneal epithelium, retinal inner nuclear cells, and ganglion cells. The enzyme protein was present in the lens epithelium adjacent to the developing ciliary body at 15.5 days postconception (E15.5) and was most strongly expressed during E17.5 to 7 days postnatally (P07). Subsequently, it declined to very low levels. The protein was also expressed in the corneal endothelial cells adjacent to the ciliary body at P07. Cyp1b1 was barely detectable in the inner ciliary epithelium before E17.5 but increased rapidly postnatally, reaching adult levels by P28. Levels of the enzyme protein in the corneal epithelium were seen from E15.5 onward, increasing sharply, and after a decrease at P07, were highest in the adult animal eye. The presence of Cyp1b1 protein in the inner nuclear layer of the retina was very low in the prenatal eye, increasing rapidly postnatally, and was highest in the adult animal eye. In the ganglion cell layer of the retina, it increased slowly from E15.5 to P07 and then rapidly reached adult levels. Interestingly, Cyp1b1 was not detected in the trabecular meshwork at any stage of development or in the adult eye. We conclude that the enzyme may play important roles in normal eye development and function in mice as in humans, and that the mouse may prove to be an excellent model for determination of the roles of CYP1B1 in human eye development and function.     

Cardiovascular effects of the aqueous extract of Moringa pterygosperma

The aqueous extract of stem bark of Moriga pterygosperma (Family Moraingaceae) was investigated for its effect on various pharmacological parameters. In cardiovascular profile at lower concentrations (1–10 ng) it produced a dose dependent positive inotropic effect (n = 3, 1.29 ± 0.021 for 10 ng) and at higher concentrations (0.1–1 μg) a dose dependent negative inotropic effect (n = 3, 0.53 ± 0.033 for 1 μg) on the isolated frog heart. It also produced a dose dependent hypotensive effect on dog blood pressure (n = 3, 82 ± 0.98 for 20 mg/kg). It failed to elicit any effect on isolated guinea-pig ileum, rat stomach fundus or frog rectus abdominis muscle.