Prevalence and Determinants of Depression among Multi Drug Resistant (MDR) TB cases registered under National Tuberculosis Elimination Program in Ahmedabad City.

Background: Multidrug-resistant tuberculosis (MDR-TB) increases the risk of depression, lowers treatment compliance leading to poor outcomes. Objectives: To (1) document the prevalence of depression among MDR-TB cases registered at tuberculosis units (TUs) of Ahmedabad city and (2) assess determinants of depression. Methodology: Adult MDR-TB patients registered at all (23) TUs of Ahmedabad city, were studied using semi-structured questionnaire along with Gujarati translated version of the Hamilton Depression Rating Scale (HAM-D) to assess the severity of depression based on 17 items. The sample size at 95% level of significance, was 251. Probability proportional to size sampling was adopted for selecting participants from each of the 23 TUs. Proportions and odds ratio with confidence interval with probability value were calculated. Results: Of 251, only 185 (73.7%) cases could be contacted. Mortality proportion among selected cases was 18.7%. More than one-fifth (22%) had ≥1 comorbidity and 9.7% had another active TB case in the family. 161 (87.1) experienced ≥1 adverse event. Financial, social, or psychological stressors were reported by 22% of cases. Based on the HAM-D scale, 16.2% suffered from depression, determinants of depression by univariate analysis showed significant association with recent family issues, discrimination, financial/other troubling issues, and the presence of adverse drug event. Conclusion: MDR-TB cases are more vulnerable for developing depression as the prevalence was 16.2% among them. Hence, cases need to be monitored closely for depression at TU as well at community level.

An Outcome-Based Follow-up Study of Cured Category I Pulmonary Tuberculosis Adult Cases from Various Tuberculosis Units under Revised National Tuberculosis Control Program from a Western Indian City.

CONTEXT: Despite the nationwide implementation of the Revised National Tuberculosis Control Program in India, adverse outcome after treatment is on rise. Program guidelines propose follow-up of cured patients for 2 years which is rarely done. OBJECTIVES: The main objectives of this study is (1) To find the response of treatment in terms of failure and drug resistance (recurrence of symptoms and mortality experience) and (2) Collect client perspective about the program and suggest the same to program managers. SUBJECTS AND METHODS: Community-based tracking of 365 cured adult Category I pulmonary tuberculosis (TB) cases drawn from three nearby TB units was done with a structured designed questionnaire. It was done to record the adverse events after 1-3 years of completion of treatment and also to record the client perspective about the program. In case of nonsurvivors, verbal autopsy was conducted by interviewing the next available relative. RESULTS: A total of 365, only 226 (60%) could be covered mainly due to wrong/incomplete address and 35 cases did not survive. Of 191 survivors who were tracked, 94.7% had sputum microscopy at the completion of treatment. Total 54 (23.9%) cases had adverse outcomes, including 31 with symptoms suggestive of TB and 23 died directly/indirectly due to TB. This cohort of cured cases, posttreatment, observed 15 times (annualized) high mortality than their counterparts. Clients or relatives largely rated the program as good/very good. CONCLUSIONS: Post-treatment tracking is must to detect an adverse outcome which is high. Most survivors and relatives of expired cases rated the program as good to very good.

Evaluation of Skill-oriented Training on Enhanced Syndromic Case Management (ESCM) of Reproductive Tract Infections / Sexually Transmitted Infections (RTI/STIs) of Care Providers from Three-tier Health-care System of Gujarat.

BACKGROUND: Enhanced syndromic case management (ESCM) deals with reproductive tract and sexually transmitted infections. Capacity building of service providers not only boosts the program but also inputs from them improve the quality of services. OBJECTIVES: To (1) identify problem areas from providers' perspectives and the gaps in knowledge and application and (2) assess the gains (if any) through pre and post-training evaluation. MATERIALS AND METHODS: A total of 121 participants (medical/para medical) from various medical colleges, district/sub-district hospitals/ community health centers, and urban dispensaries across Gujarat were trained at a teaching institute. Trainings were of 2-3 days duration involving different learning methodology. Pre- and post-training evaluation were done on a designed pro forma and data were entered in MS office Excel 2007. Gains in knowledge/skills if any were assessed by comparing pre-/post-evaluation responses and applying test of significance (x(2) test). OBSERVATIONS: Out of total 121 participants, half (60) were doctors and the rest were paramedics [staff nurse (SN) and lab technicians (LT)]. Doctors revealed significant gain in basics of reproductive tract infections (RTI) and sexually transmitted infections (STI), syndrome identification, STI/HIV co-infection, and ESCM and less gain in asymptomatic STI/ complications, vulnerability, male reproductive organs, causes of vaginal/urethral discharge, STI complications, cervical cancer screening, and limitation of syndromic management. Gain was statistically significant in basics of RTI/STI amongst adolescent in paramedics; lab technicians showed significant gain in knowledge of laboratory-related areas. CONCLUSION: Assessment revealed (1) poor baseline knowledge and (2) gains following training sometimes significant and other times not significant even in core areas. Quality monitoring and contents/ methodologies modification are essential for robust trainings. Gains in skills could not be assessed through this evaluation.

Preparation and evaluation of sublingual tablets of zolmitriptan.

AIM: Zolmitriptan is a 5-HT receptor agonist (1B/1D). It is used in the acute treatment of migraine having low bioavailability about 40% orally due to hepatic first pass metabolism. The purpose of the present research was to formulate fast acting sublingual tablets of zolmitriptan. MATERIALS AND METHODS: Sublingual tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as super disintegrating polymers and citric acid, tartaric acid and camphor as permeation enhancers by direct compressible technique and evaluated for weight variation, thickness, friability, content uniformity, hardness, disintegration time, wetting time, in-vitro drug release, in-vitro and ex-vivo permeation study. Stability study of optimized formulation was performed as per ICH (International Conference on Harmonisation) guideline. RESULTS: The in-vitro disintegration time of the optimized formulation (D5) was 9 ± 2 s and all formulations showed 100% of dissolution within 6 ± 2 min. Formulation containing 4% of gellan gum (D5) showed highest disintegration and 2% of citric acid formulation (P3) showed highest permeation 88% within 30 min and ex-vivo permeation was 52% within 30 min. Optimized formulation was stable for 1 month during stability study as per ICH guideline. CONCLUSION: The sublingual tablet formulation gives better results using natural super disintegrant for fast onset of action.

Formulation and evaluation of liquisolid compacts for olmesartan medoxomil.

Olmesartan medoxomil is an angiotensin type II receptor blocker, antihypertensive agent, administered orally. It is highly lipophilic (log P 5.5) and a poorly water-soluble drug with absolute bioavailability of 26%. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. The objective of the present investigation was to develop liquisolid compacts for olmesartan medoxomil to improve the dissolution rate. Liquisolid compacts were prepared using Acrysol El 135 as a solvent, Avicel PH 102, Fujicalin and Neusilin as carrier materials, and Aerosil as coating material in different ratios. The interaction between drug and excipients was characterized by DSC and FT-IR studies, which showed that there is no interaction between drug and excipients. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial limits. The dissolution studies for liquisolid compacts and conventional formulations were carried out, and it was found that liquisolid compacts with 80% w/w of Acrysol EL 135 to the drug showed significant higher drug release rates than conventional tablets. Amongst carriers used Fujicalin and Neusilin were found to be more effective carrier materials for liquid adsorption.

Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement.

Olmesartan medoxomil (OLM) is an angiotensin II receptor blocker (ARB) antihypertensive agent administered orally that has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 µg/ml). The aim of the present investigation was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral absorption of OLM. The solubility of OLM in various oils, surfactants, and cosurfactants was determined. Pseudoternary phase diagrams were constructed using Acrysol EL 135, Tween 80, Transcutol P, and distilled water to identify the efficient self-microemulsification region. Prepared SMEDDS was further evaluated for its emulsification time, drug content, optical clarity, droplet size, zeta potential, in vitro dissolution, and in vitro and ex vivo drug diffusion study. The optimized formulation S2 contained OLM (20 mg), Tween 80 (33%v/v), Transcutol P (33%v/v), and Acrysol EL 135 (34%v/v) had shown the smallest particle size, maximum solubility, less emulsification time, good optical clarity, and in vitro release. The in vitro and ex vivo diffusion rate of the drug from the SMEDDS was significantly higher than that of the plain drug suspension. It was concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.

Formulation and evaluation of sublingual tablets containing Sumatriptan succinate.

OBJECTIVE: Sumatriptan succinate is a selective 5-hydroxytryptamine-1 receptor agonist effective in the acute treatment of migraine headaches, having low bioavailability of about 15% orally due to first-pass metabolism. The purpose of this research was to mask the intensely bitter taste of Sumatriptan succinate and to formulate fast-acting, taste-masked sublingual tablet formulation. MATERIALS AND METHODS: Taste masking was performed by solid dispersion method with mannitol and ion exchange with Kyron T 114 because it releases the drug in salivary pH. The resultant batches were evaluated for in-vivo taste masking as well compatability study (Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC)). For a better feel in the mouth, menthol and sweetener Na saccharine were added to the tablet formulation. The tablets were prepared by direct compression and evaluated for weight variation, thickness, friability, drug content, hardness, disintegration time, wetting time, in vitro drug release, and in vitro permeation study. RESULTS AND DISCUSSION: Optimized batches disintegrated in vitro within 28-34 s. Maximum drug release could be achieved with in 10 min for the solid dispersion batches and 14-15 min for the ion-exchange batches with Kyron T 114. The optimized tablet formulation showed better taste and the formulated sublingual tablets may act as a potential alternate for the Sumatriptan succinate oral tablet. CONCLUSION: Sumatriptan succinate can be successfully taste-masked by both the solid dispersion method using mannitol by the melting method and Ion exchange resin with Kyron T114. It was also concluded that prepared formulation improve bioavailability by prevention of first pass metabolism.

Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist.

PURPOSE: The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. MATERIALS AND METHODS: Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 2(3) full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. RESULTS: Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug-excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. CONCLUSION: It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease.

Development and validation of the liquid chromatography-tandem mass spectrometry method for quantitative estimation of candesartan from human plasma.

INTRODUCTION: A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for estimation of candesartan in human plasma using the protein precipitation technique. MATERIALS AND METHODS: The chromatographic separation was performed on reverse phase using a Betasil C8 (100 × 2.1 mm) 5-µm column, mobile phase of methanol:ammonium tri-floro acetate buffer with formic acid (60:40 v/v) and flow rate of 0.45 ml/min. The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The mass transitions m/z 441.2 → 263.2 and 260.2 → 116.1 were used to measure candesartan by using propranolol as an internal standard. RESULTS: The linearity of the developed method was achieved in the range of 1.2-1030 ng/ml (r(2) ≥ 0.9996) for candesartan. CONCLUSION: The developed method is simple, rapid, accurate, cost-effective and specific; hence, it can be applied for routine analysis in pharmaceutical industries.

Formulation and evaluation of controlled-release tablet of zolpidem tartrate by melt granulation technique.

The present investigation describes the influence of the concentration of PEG 6000 as a melt binder and ratio of HPMC K4M : PVP on Zolpidem tartrate controlled-release tablet formulations using 3(2) full factorial design. The ratio of HPMC K4M and PVP K30 (X(1)) and the concentration of melt binder (X(2)) were selected as independent variables, and drug release at 1 hr (Q(1)), 4 hr (Q(4)), 8 hr (Q(8)), diffusion coefficient (n), and release rate constant (K) were selected as a dependent variable. Tablets were prepared by melt granulation technique and evaluated for various evaluation parameters. It was observed that concentration of melt binder had significant effect on Q(1), Q(4), n, and K Binder concentration 25% w/w was found optimum. Optimized formulation (F(7)) showed good similarity with theoretical profile of drug. The X(2) variable had a significant effect on dependent variables, and the X(1) variable had no significant effect on dependent variables.

Formulation and evaluation of transdermal patch of repaglinide.

Repaglinide has the half life of 1 hour, and bioavailability in the body is 56% due to first-pass metabolism. The total daily dose of Repaglinide is 16 mg (e.g., 4 mg four times daily depending on meal patterns); hence, it required frequent dosing. Transdermal patch of Repaglinide was prepared to sustain the release and improve bioavailability of drug and patient compliance. Different formulations were prepared by varying the grades of HPMC and concentration of PVP K30 by solvent casting method. The prepared formulations were evaluated for various parameters like thickness, tensile strength, folding endurance, % elongation, % moisture content, % moisture uptake, % drug content, in vitro drug release, in vitro permeation, and drug excipient compatibility. A 3(2) full factorial design was applied to check the effect of varying the grades of HPMC (X(1)) and PVP concentration (X(2)) on the responses, that is, tensile strength, percentage drug released in 1 hr (Q(1)), 9 hr (Q(9)), and diffusion coefficient as a dependent variables. In vitro release data were fitted to various models to ascertain kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. The results of the F2 statistics between factorial design batches and theoretical profile were used to select optimized batch. Batch F6 was considered optimum batch which contained HPMC K100 and PVP (1.5%), showed release 92.343% up to 12 hr, and was more similar to the theoretical predicted dissolution profile (f(2) = 69.187).

Floating matrix tablets of domperidone formulation and optimization using simplex lattice design.

The purpose of this research was to prepare a floating matrix tablet containing domperidone as a model drug. Polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) were evaluated for matrix-forming properties. A simplex lattice design was applied to systemically optimize the drug release profile. The amounts of PEO WSR 303, HPMC K15M and sodium bicarbonate were selected as independent variables and floating lag time, time required to release 50% of drug (t50) and 80% of drug (t80), diffusion coefficient (n) and release rate (k) as dependent variables. The amount of PEO and HPMC both had significant influence on the dependent variables. It was found that the content of PEO had dominating role as drug release controlling factor, but using suitable concentration of sodium bicarbonate, one can tailor the desired drug release from hydrophilic matrixes. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). The tablets of promising formulation were found to be stable for 3 months under accelerated (40°C / 75% RH) stability testing.

Thermoreversible mucoadhesive ophthalmic in situ hydrogel: Design and optimization using a combination of polymers.

The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 3(2) full factorial design was employed with two polymers: Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 33-36 °C. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.

Gastric floating matrix tablets: design and optimization using combination of polymers.

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.