Luliconazole Nail Lacquer for the Treatment of Onychomycosis: Formulation, Characterization and In Vitro and Ex Vivo Evaluation.

Onychomycosis is the most common fungal infection of the nail affecting the skin under the fingertips and the toes. Currently, available therapy for onychomycosis includes oral and topical therapies, either alone or in combination. Oral antifungal medication has been associated with poor drug bioavailability and potential gastrointestinal and systemic side effects. The objective of this study was to prepare and evaluate the luliconazole nail lacquer (LCZ-NL) for the effective treatment of onychomycosis. In the current work, LCZ-NL was formulated in combination with penetration enhancers to overcome poor penetration. A 32 full factorial formulation design of experiment (DOE) was applied for optimization of batches with consideration of dependent (drying time, viscosity, and rate of drug diffusion) and independent (solvent ratio and film former ratio) variables. The optimized formulation was selected based on drying time, viscosity, and rate of drug diffusion. The optimized formulation was further evaluated for % non-volatile content assay, smoothness of flow, water resistance, drug content, scanning electron microscope (SEM), atomic force microscope (AFM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), in vitro drug release, ex vivo transungual permeation, antifungal efficacy, and stability study. The optimized LCZ-NL contained 70:30 solvent ratio and 1:1 film former ratio and was found to have ~ 1.79-fold higher rate of drug diffusion in comparison with LULY™. DSC and XRD studies confirmed that luliconazole retains its crystalline property in the prepared formulation. Antifungal study against Trichophyton spp. showed that LCZ-NL has comparatively higher growth inhibition than LULY™. Hence, developed LCZ-NL can be a promising topical drug delivery system for treating onychomycosis.

Systematic development and characterization of curcumin-loaded nanogel for topical application.

Curcumin (CUR) conventional formulation has poor oral bioavailability due to low solubility and low stability. Also, it extensively undergoes first-pass-metabolism showing low biological activity. The present work focuses on the systematic development and characterization of CUR-loaded Nanostructured Lipid Carrier (CUR-NLCs) having promising topical applications for skin diseases such as psoriasis. CUR-NLCs were prepared by using high-speed homogenization method. Quality by design approach was exploited to select out Critical Process Parameters i.e. homogenization speed (X1), homogenization time (X2), amount of lipid (X3), solid lipids (SL): liquid lipids (LL) (X4), and surfactant conc. (X5) using Plackett-Burman design and for obtaining critical quality attributes i.e. particle size (Y1) and entrapment efficiency (Y2) using Box-Behnken design. The developed NLCs were found to be nano-metric in size (189.4 ± 2.6 nm) with a low polydispersity index (0.262 ± 0.24), zeta potential (-21.45 ± 1.3 mV), and showed good encapsulation efficiency (86.72 ± 09%). Surface morphology determined by SEM and AFM revealed the spherical shape of the NLCs with a smooth surface. XRD studies showed NLCs in the amorphous state. After incorporation of NLCs into a nanogel, it was characterized for pH, rheological behavior, spreadability, in vitro occlusion, and in vitro release kinetics. The drug release from NLC in 24 h was found to be 60.2 ± 0.45% indicating a sustained release pattern. Ex vivo permeation studies revealed a good permeation flux (0.453 ± 0.76 µg/cm2.h) and retention (60.2 ± 0.45%) of CUR in the skin epidermis. Thus, developed CUR-NLCs can be a potential delivery system and a promising therapeutic approach for the effective treatment of psoriasis.

Cd2+ + Cr6+ causes toxic effects on chromosomal development of microspore in Carthamus tinctorius.

Intra-category hybrids of Carthamus tinctorius were analyzed for the genetic toxicity in detail for effect of Cd2+ + Cr6+ on reproductive biology of Carthamus tinctorius. Five partially tolerant and five non-tolerant accessions of Carthamus tinctorius after screening were crossed to produce intra-category hybrid. These two heavy metals in combination influenced antagonistically first as well as second meiotic divisions inducing various kinds of anomalies and reduced the number of pollen grains per anther and significantly increased pollen sterility. A differential response for the amount of meiotic irregularity was recorded between different treated sets of hybrids in (Cd + Cr) treated sets. This could be due to differential response of the genotypes for the same concentration of (Cd + Cr). These two heavy metals in combination reduced the number of pollen grains per anther and significantly increased pollen sterility.

Tuberculosis Treated by Multiple Drugs: An Overview.

BACKGROUND: Tuberculosis is an infection and caused by gentle growing bacteria. The Internet provides opportunities for people with tuberculosis (TB) to connect with one another to address these challenges. OBJECTIVE: The aim of this paper is to introduce readers to the platforms on which Tuberculosis participants interact, to discuss reasons for and risks associated with TB-related activity, and to review research related to the potential impact of individual participation on TB outcomes. METHODS: Research and online content related to Tuberculosis online activity is reviewed, however, the difficulty in accurate prescribing and adhering to these protocols and the emergence of M. tuberculosis strains resistant to multiple drugs and drug-drug interactions that interfere with optimal treatment of Tuberculosis and co-infected patients with the different disease has generated a pressing need for improved Tuberculosis therapies. RESULTS: Together with the ominous global burden of Tuberculosis, those shortcomings of current medication have contributed to a renewed interest in the development of improved drugs and protocols for the medication of Tuberculosis. This article features obstacles related with the enhanced utilization of existing drugs and difficulties related with the advancement of enhanced products, concentrating on perspectives characteristic in Tuberculosis drug clinical improvement. The participation includes peer support, advocacy, self-expression, seeking and sharing TB information, improving approaches to Tuberculosis data management, and humour. CONCLUSION: This article highlights hurdles related to the optimised use of existing drugs and challenges related to the development of improved products, focusing on aspects inherent in Tuberculosis drug clinical development. Concluding comments offer processes for more efficient development of Tuberculosis therapies and increase the quality of life.

Elevated Blood Pressure and Its Associated Risk Factors among Adolescents of a North Indian City - A Cross-sectional Study.

CONTEXT: Amidst the uncertainty in childhood blood pressure (BP) thresholds, besides the ambiguity in levels and duration of BP elevation causing organ damage, hypertension is present in substantial number of asymptomatic children and adolescents with only a few studies disclosing the setup. With projection of deaths due to noncommunicable diseases in 2030 rising to 52 million, it is necessary to know about the knowledge of present adolescents about BP and its modifiable risk factors. AIMS: (1) To assess the prevalence of elevated BP among adolescents and to ascertain the associated risk factors. (2) To assess adolescent's knowledge about BP and its modifiable factors. SETTINGS AND DESIGN: A community-based cross-sectional study was conducted on school going adolescents of Lucknow, from September 2014 to August 2015. SUBJECTS AND METHODS: BP, height, and weight were measured following standard protocols, Centers for Disease Control and Prevention charts for finding respective cut-off values and oral questionnaire for assessing lifestyle risk factors were used. STATISTICAL ANALYSIS: Chi-square, unpaired t-test, and logistic regression were used. RESULTS: Of the 1041 participants, elevated BP (BP percentile ≥90) was prevalent in 24.2%. On regression, factors such as obesity (adjusted odds ratio [aOR] = 5.8, 95% confidence interval [CI] = 3.6-9.4), low fruit diet (aOR = 3.3, 95% CI = 2.1-5.4), and frequent junk food consumption (aOR = 1.9, 95% CI = 1.3-2.8) raised the odds of elevated BP while it was lowered by being physically active (aOR = 0.67, 95% CI = 0.46-0.97). Of 86.3% of children (n = 898) who were fathomed of BP, only less than third (33% and 21.9%) acquainted of BP raising and lowering practices, respectively. CONCLUSIONS: Prevalence of high BP is colossal with only a few children knowing its amendable nature. Strenuous efforts targeting detrimental behaviors and imparting the sense of healthy lifestyle enhancing practices are vital to control this epidemic.

High-risk sexual behavior among people living with HIV/AIDS attending tertiary care hospitals in district of Northern India.

CONTEXT: Prevention with a positive approach has been advocated as one of the main strategies to diminish the new instances of HIV and the target are those who are engaged in high-risk sexual behavior. Therefore, understanding the risky behaviors of the HIV-infected individual is important. AIMS: This study aimed to assess the prevalence and the predictors of high-risk sexual behavior among people living with HIV/AIDS (PLHA). SETTINGS AND DESIGN: A hospital-based cross-sectional study was conducted at antiretroviral therapy centers of two tertiary care hospitals in Lucknow. MATERIALS AND METHODS: A total of 322 HIV-positive patients were interviewed about their sexual behaviors during last 3 months using a pretested questionnaire. STATISTICAL ANALYSIS USED: Probability (p) was calculated to test for statistical significance at 5% level of significance. Association between risk factors and high-risk sexual behavior was determined using bivariate analysis followed by multivariate logistic regression. RESULTS: Prevalence of high-risk sexual behavior was 24.5%. Of these patients, multiple sexual partners were reported by 67.3% whereas about 46.9% were engaged in unprotected sex. Multivariate logistic regression analysis revealed that high-risk sexual behavior was significantly associated with nonsupporting attitude of spouse (odds ratio [OR]: 18; 95% confidence interval [CI]: 1.4-225.5; P = 0.02) and alcohol consumption (OR: 9.3; 95% CI: 2.4-35.4; P = 0.001). CONCLUSIONS: Specific intervention addressing alcohol consumption and encouragement of spouse and family support should be integrated in the routine HIV/AIDS care and treatment apart from HIV transmission and prevention knowledge.

Nonadherence to Antiretroviral Therapy Among People Living with HIV/AIDS Attending Two Tertiary Care Hospitals in District of Northern India.

INTRODUCTION: Adherence to antiretroviral therapy is a principal predictor for the success of human immunodeficiency virus (HIV) treatment. It remains as a challenge to acquired immunodeficiency syndrome (AIDS) treatment and care with the widespread of the associated risks. Therefore, study aims to assess nonadherence level and factors associated with nonadherence to ART among people living with HIV/AIDS (PLHA). MATERIALS AND METHODS: A hospital-based, cross-sectional study was conducted at two tertiary care hospital of Lucknow. A total of 322 adult HIV-positive patients registered in the ART center were included. Systematic random sampling was used to recruit patients. Nonadherence was assessed on the basis of pill count method. RESULTS: A total of 10.9% of patients were found to be nonadherent to ART. Principal causes cited were being busy with other work (40.0%), felt sick or ill (28.5%), not having money (14.2%), and being away from home (11.4). Multivariate logistic regression analysis revealed that nonadherence was significantly associated with nonbeneficial perceptions towards ART (odds ratio (OR) 18.5; 95% confidence interval (CI) 3.2-106.6; P = 0.001), being counseled for adherence for more than 3 months (OR 13.9; 95% CI 1.6-118.9; P = 0.01), presence of depression (OR 2.6; 95% CI 1.0-6.7; P = 0.04), and those who were not satisfied with healthcare facilities (OR 5.63; 95% CI 1.88-16.84; P = 0.00). CONCLUSION: Although adherence to ART varies between individuals and over time, the factors that affect nonadherence can be addressed with proper periodic counseling and motivation of patients and their family members. Adherence to highly active antiretroviral therapy (HAART) could delay the progression of this lethal disease and minimize the risk of developing drug resistance.

Determinants of prelacteal feeding in rural northern India.

BACKGROUND: Prelacteal feeding is an underestimated problem in a developing country like India, where infant mortality rate is quite high. The present study tried to find out the factors determining prelacteal feeding in rural areas of north India. METHODS: A crosssectional study was conducted among recently delivered women of rural Uttar Pradesh, India. Multistage random sampling was used for selecting villages. From them, 352 recently delivered women were selected as the subjects, following systematic random sampling. Chi-square test and logistic regression were used to find out the predictors for prelacteal feeding. RESULTS: Overall, 40.1% of mothers gave prelacteal feeding to their newborn. Factors significantly associated with such practice, after simple logistic regression, were age, caste, socioeconomic status, and place of delivery. At multivariate level, age (odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.13-2.74), caste and place of delivery (OR = 2.23, 95% CI = 1.21-4.10) were found to determine prelacteal feeding significantly, indicating that young age, high caste, and home deliveries could affect the practice positively. CONCLUSIONS: The problem of prelacteal feeding is still prevalent in rural India. Age, caste, and place of delivery were associated with the problem. For ensuring neonatal health, the problem should be addressed with due gravity, with emphasis on exclusive breast feeding.

Factors associated with the preference for delivery at the government hospitals in rural areas of Lucknow district in Uttar Pradesh.

For assuring safe maternal and newborn health, institutional delivery was given paramount importance. In India, in spite of several efforts, lesser than 40% deliveries are conducted at health facilities, mostly at private sector. The present cross-sectional study aimed to find out the determinants of preference for delivery at government hospitals in rural areas of Lucknow, a district in Uttar Pradesh. Multistage random sampling was used for selecting villages. From them, 352 recently delivered women were selected, following systematic random sampling. Overall, 84.9% of deliveries were conducted at health institutions. Out of them, 79.3% were at government hospitals. Applying multivariate logistic regression, Hindu women (odd's ratio [OR] = 3.205), women belonging to lower socio-economic class (OR = 4.630) and late registered women (OR = 2.320) were found to be more likely to deliver at government hospitals. Attention should be given to religion, social status and timing of registration for ensuring higher fraction of deliveries at government set-up.

CNS drug targeting: have we travelled in right path?

BACKGROUND: Brain disorders, their prevalence and central nervous system (CNS) targeting are now at the rise. However, complexities of blood brain barrier (BBB) have limited the success of CNS targeting. Basic criteria necessary for passive diffusion were believed to influence the CNS drug delivery. However, often, BBB transportation has differed from the dogma of basic criteria. PURPOSE: This communication resets the extent to which basic criteria influence the brain delivery, through commanding examples. Further, it appraises the intervention of ABC transporters in BBB transportation, with a special emphasis on P-glycoprotein; and also brings forth the successful CNS transportation of therapeutics achieved through chimeric peptide technology. As a right path to travel, it flickers light on the novel CNS molecular drug targets/biomarkers which are specially expressed by diseased cells. CONCLUSION: Screening for right molecular target is of great importance for cost and time effective drug discovery process. The principle of chimeric peptide technology should be applied for CNS targeting; and every diseased cell should be screened for its biomarker. Thanks to glycan/lectin arrays technique which scans expression pattern of transporter and their possible ligands, and paves way for a new dimensional research.

A comparison between use of spray and freeze drying techniques for preparation of solid self-microemulsifying formulation of valsartan and in vitro and in vivo evaluation.

The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug in in vitro and in vivo conditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.

Evaluation of hydrophilic, hydrophobic and waxy matrix excipients for sustained release tablets of venlafaxine hydrochloride.

OBJECTIVE: Venlafaxine is freely soluble In water and administered orally as hydrochloride salt In two to three divided doses. In the present investigation different release retarding matrices have been evaluated for sustained release of venlafaxine hydrochloride (VH) from the formulated tablets. MATERIALS AND METHODS: Sustained release matrix tablets were formulated using different hydrophilic, hydrophobic and waxy materials as matrix formers. Tableting was done by pre-compression, direct compression and hot melt granulation depending on the type of matrix material used and evaluated for different tests. The formulated tablets were compared with commercial venlafaxine products. In vitro drug dissolution profiles were fitted In different mathematical models to elucidate the release mechanism. RESULTS: Dissolution data showed that commercial formulations Venlor XR(®) and Venfax PR(®) released the entire drug withIn 8 h where as the formulated tablets with hydroxypropylmethylcellulose (HPMC) and cetyl alcohol as matrix formers provided sustained release of drug for 14-15 h. The release was found to follow Hixson Crowel and Higuchi kinetics for HPMC and cetyl alcohol tablets, respectively. CONCLUSION: The developed matrix tablet formulations with HPMC and cetyl alcohol provided sustained release profiles for prolonged periods than commercial formulations.

Evaluation of metronidazole nanofibers in patients with chronic periodontitis: A clinical study.

AIM: Prevention of periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found to be inadequate in achieving periodontal health in chronic periodontitis, local antimicrobial agents are used as an adjunct to scaling and root planing (SRP), which produces encouraging results. In the present study, an attempt was made to develop a low-dose controlled-release delivery system for the treatment of periodontal infections. A new sustained release drug system of poly e-caprolactone (PCL) nanofibers containing metronidazole (MET) was successfully electrospun and evaluated clinically for periodontal diseases. The retentive nanofibres were shown to provide a controlled delivery of the drugs. MATERIALS AND METHODS: Nanofibers were prepared with MET in PCL by electrospinning technique. The drug-coated nanofibers provided sustained effect up to a period of 11 days (264 h) and followed first-order release. Forty sites in seven patients (four females and three males) with chronic periodontitis (5-8 mm probing depth) were allocated in two experimental treatment groups: Group A treated with SRP + MET nanofibers and Group B treated with SRP alone (control group). All these patients were evaluated clinically for probing depth (PD), plaque index (PI), and gingival index (GI). RESULTS: Both the treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PD, PI, and GI. CONCLUSION: Combination of SRP + MET nanofibers (Group A) resulted in added benefits, compared to the control group.

Floating microspheres of cimetidine: formulation, characterization and in vitro evaluation.

The present study involves preparation and evaluation of floating microspheres with cimetidine as model drug for prolongation of gastric residence time. The microspheres were prepared by the solvent evaporation method using polymers hydroxypropylmethyl cellulose and ethyl cellulose. The shape and surface morphology of prepared microspheres were characterized by optical and scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression method. Effects of the stirring rate during preparation, polymer concentration, solvent composition and dissolution medium on the size of microspheres and drug release were also observed. The prepared microspheres exhibited prolonged drug release (approximately 8 h) and remained buoyant for > 10 h. The mean particle size increased and the drug release rate decreased at higher polymer concentration. No significant effect of the stirring rate during preparation on drug release was observed. In vitro studies demonstrated diffusion-controlled drug release from the microspheres.