RESUMO
Fusarium wilt (FW) is the most severe soil-borne disease of chickpea that causes yield losses up to 100%. To improve FW resistance in JG 11, a high-yielding variety that became susceptible to FW, we used WR 315 as the donor parent and followed the pedigree breeding method. Based on disease resistance and yield performance, four lines were evaluated in station trials during 2017-2018 and 2018-2019 at Kalaburagi, India. Further, two lines, namely, Kalaburagi chickpea desi 5 (KCD 5) and KCD 11, which possesses the resistance allele for a specific single-nucleotide polymorphism marker linked with FW resistance, were evaluated across six different locations (Bidar, Kalaburagi, Raichur, Siruguppa, Bhimarayanagudi and Hagari) over a span of 3 years (2020-2021, 2021-2022 and 2022-2023). KCD 11 exhibited notable performance, showcasing yield advantages of 8.67%, 11.26% and 23.88% over JG 11, and the regional checks Super Annigeri 1 (SA 1) and Annigeri 1, respectively, with enhanced FW resistance in wilt sick plot. Further, KCD 11 outperformed JG 11, SA 1 and Annigeri 1 in multi-location trials conducted across three seasons in the North Eastern Transition Zone, North Eastern Dry Zone, and North Dry Zones of Karnataka. KCD 11 was also tested in trials conducted by All India Coordinated Research Project on chickpea and was also nominated for state varietal trials for its release as a FW-resistant and high-yielding variety. The selected line is anticipated to cater the needs of chickpea growers with the dual advantage of yield increment and disease resistance.
Assuntos
Cicer , Resistência à Doença , Fusarium , Melhoramento Vegetal , Doenças das Plantas , Cicer/microbiologia , Cicer/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Fusarium/patogenicidade , Fusarium/fisiologia , Resistência à Doença/genética , Melhoramento Vegetal/métodos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background: Newer therapies, such as dipeptidyl peptidase-IV inhibitors, are increasingly being used in the treatment of type 2 diabetes mellitus (T2DM). Teneligliptin, a DPP4 inhibitor, currently commonly used as monotherapy or as add-on therapy, was generally well tolerated in patients with T2DM during clinical trials. No AEs related to QT prolongation were detected with 40 mg/day of teneligliptin, but were seen at a supratherapeutic dose of 160 mg/day. Aims and objective: To evaluate the safety of teneligliptin in type 2 diabetes patients with respect to QTc prolongation. Methodology: This was an open-label, prospective, multi-centric trial conducted in patients with T2DM aged ≥18 to ≤65 years with a hemoglobin A1c (HbA1c) ≥7.0% and gliptin naïve. Teneligliptin 20 mg once a day was added to the standard treatment. The dose of teneligliptin was increased to 40 mg once a day if required, on the basis of glycemic parameters. Twelve-lead ECG was recorded at baseline and follow-up visits. The QTc was calculated by using the Bazett's formula (QTc=QT/âRR). Results: The mean QT interval at screening (Visit 1, Day 0, baseline ECG) was 0.33±0.07 seconds, while at visit 2 (Day 1, post 2 hours of Teneligliptin dosing) it was 0.32±0.04 seconds, at visit 3 (Day 15) it was 0.32±0.04 seconds, and at visit 4 (Day 90) it was 0.32±0.03 seconds. The mean QTc interval at baseline was 0.37±0.04 seconds, while at visit 2 it was 0.37±0.04 seconds, at visit 3 it was 0.37±0.03 seconds, and at visit 4 it was 0.37±0.03 seconds. There was a significant reduction in fasting blood glucose (P=0.002), postprandial blood glucose (P<0.001), and HbA1c (P<0.001) at the end of the 3 months as compared to baseline. Conclusion: Teneligliptin at a therapeutic dose of 20 mg/day or 40 mg/day improved glycemic parameters significantly and did not cause QT/QTc interval prolongation.
RESUMO
A multicenter trial in India undergoes review by Institutional Ethics Committees (IECs) of all participating institutions. The failure to obtain approval even from a single institution's IEC creates a situation of inequitable access to clinical trials. The dichotomy in decisions of different IECs is attributed to lack of standardization and accountability in their functioning. The registration of IECs with Central Drugs Standard Control Organization notwithstanding, the current model of IEC review has failed to ensure uniformity in IEC decisions in multicenter trials. Alternative models that allow central review of multicenter clinical trials should be explored.
Assuntos
Comitês de Ética em Pesquisa , Comissão de Ética , Estudos Multicêntricos como Assunto , Bioética , Humanos , ÍndiaRESUMO
It is recommended that for effective utilization of spent hen meat, it should be converted into value added or shelf stable meat products. Since we are lacking in cold chain facilities, therefore there is imperative need to develop shelf stable meat products. The present study was envisaged with the objective to develop dehydrated chicken meat rings utilizing spent hen meat with different extenders. A basic formulation and processing conditions were standardized for dehydrated chicken meat rings. Extenders such as rice flour, barnyard millet flour and texturized soy granule powder at 5, 10 and 15 % levels were incorporated separately replacing the lean meat in pre standardized dehydrated chicken meat ring formulation. On the basis of physico-chemical properties and sensory scores optimum level of incorporation was adjudged as 10 %, 10 % and 5 % for rice flour, barnyard millet flour and texturized soy granule powder respectively. Products with optimum level of extenders were analysed for physico-chemical and sensory attributes. It was found that a good quality dehydrated chicken meat rings can be prepared by utilizing spent hen meat at 90 % level, potato starch 3 % and refined wheat flour 7 % along with spices, condiments, common salt and STPP. Addition of an optimum level of different extenders such as rice flour (10 %), barnyard millet flour (10 %) and TSGP (5 %) separately replacing lean meat in the formulation can give acceptable quality of the product. Rice flour was found to be the best among the three extenders studied as per the sensory evaluation.
RESUMO
UNLABELLED: During pregnancy or postpartum period many women will experience some degree of pelvic girdle pain (PGP). In India, there is no information about the PGP prevalence and its associated factors evaluated during postpartum period. PURPOSE: To reveal the prevalence of PGP postpartum in Indian women and identify associated factors with PGP postpartum. METHODS: In this cross-sectional study, 284 postpartum women completed a questionnaire and underwent clinical examinations. The clinical examination included pain provocation tests for the pelvic as well as the active straight leg raise (ASLR) test. Possible associating factors were studied by using nonparametric tests and logistic regression analysis. RESULTS: A total of 116 postpartum women (41%) had reported PGP at the time of the examination. A stepwise logistic regression analysis was performed to reveal associated factors. In the final model, factors such as (1) Caesarean delivery (adjusted OR, 2.0; 95% CI, 1.3-4.9); (2) ASLR test score ≥4 (adjusted OR, 2.3; 95% CI, 1.2-3.3); (3) Unilateral P4 test (adjusted OR, 1.8; 95% CI, 1.1-3.0); and (4) Sitting position during feeding (adjusted OR, 1.5; 95% CI, 0.9-2.8) were associated with the PGP. CONCLUSION: We found a high prevalence of PGP in Indian women during the first three months of postpartum period. Our finding suggests that unilateral posterior pelvic pain provocation test (P4), ASLR test score ≥4, caesarean section delivery and sitting in breast-feeding posture were associated with increased risk of PGP during postpartum.
Assuntos
Dor da Cintura Pélvica/epidemiologia , Adulto , Aleitamento Materno/efeitos adversos , Cesárea/efeitos adversos , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Modelos Logísticos , Razão de Chances , Medição da Dor , Dor da Cintura Pélvica/diagnóstico , Período Pós-Parto , Postura , Gravidez , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: During pregnancy or postpartum period, several women experience some degree of pelvic girdle pain (PGP). In India, information is lacking about the prevalence and possible risk factors of PGP evaluated during postpartum period. This study aims to determine the prevalence of PGP in postpartum women who underwent vaginal or caesarean mode of delivery and to estimate possible associated factors with or without PGP in both modes of deliveries. METHODS: In this cross-sectional study, 284 postpartum women answered questionnaires and underwent clinical examinations. Clinical examination included pain provocation tests for the pelvis as well as the active straight leg raise (ASLR) test. Probable associated factors were studied using non-parametric tests and logistic regression analysis. RESULTS: In this study of 284 women, 41% reported pain in the pelvic girdle during postpartum period. Overall, 33% of the women experienced PGP after caesarean delivery as compared with 8.3% of women after vaginal delivery. Low back pain (LBP) before pregnancy, parity, active straight leg raise test score ≥ 4, bilateral P4 test, and sitting position during breast-feeding were significantly associated with vaginal delivery group and caesarean delivery group during postpartum period. In both modes of delivery, the association of PGP with these common factors remained after adjustment for other study factors. CONCLUSION: We found high prevalence of PGP in women who had caesarean delivery than those who had a vaginal delivery. Our finding suggests that, during postpartum period, LBP before pregnancy, parity, ASLR test score ≥ 4, bilateral P4 test, and sitting position during breast-feeding were significantly associated with increased risk of PGP in both vaginal and caesarean modes of deliveries, but further studies are needed for definitive conclusions.
Assuntos
Parto Obstétrico , Parto , Dor Pélvica/epidemiologia , Período Pós-Parto , Adulto , Aleitamento Materno , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Dor Lombar/epidemiologia , Exame Neurológico , Paridade , Postura/fisiologia , Gravidez , Adulto JovemRESUMO
Pantoprazole sodium is a proton pump inhibitor used to treat peptic ulcers and gastroesophageal reflux. This drug is unstable in acid solution, in the presence of salts, as well as in UVC radiation. Hence the aim of present study was to develop microparticles that will protect the drug from degradation in gastric acid and increase its photostability. Microparticles were prepared by the solvent evaporation method using Eudragit S 100 as enteric polymer by varying drug: polymer ratios ranging from 1:1 to 1:4. The developed microparticles were characterized for surface morphology, particle size, encapsulation efficiency, and stability in acidic media. Microparticles obtained with the ratio 1:4 were spherical, had a smooth surface, and showed the highest percent entrapment of 67 ± 2.1%. Microparticles showed uniform size distribution; about 87% of microparticles were in the size range of 50 to 75 µm. In vitro dissolution studies showed no drug release in acidic media; further prolonged drug release for a period of 9 h was obtained with a 1:4 in phosphate buffer pH 7.4 following Higuchi release kinetics with regression value of 0.9896. Photodegradation studies were performed in solar light and in UV light at 254 nm and 366 nm for 7 days. The concentration of drug was determined spectrophotometrically at 290 nm. Percent degradation under solar light for pure drug was 25%, and no significant degradation was seen in drug-loaded microparticles. Degradation under UV radiation 254 nm and 366 nm was found to be 38.6% and 12.11% and 35.11% and 6.13% for pure drug and drug-loaded microparticles respectively. LAY ABSTRACT: Pantoprazole sodium is widely used in treatment of acid-related disorders and management of gastroesophageal reflux diseases. It is an acid-labile drug that degrades in the stomach at pH 1-2 and is highly unstable in UVC light. Hence the aim of research work was to improve photostability of pantoprazole and protect it from the acidic environment by loading in gastroresistant microparticles. Various batches of microparticles were prepared by the solvent evaporation method using Eudragit S 100 as an enteric polymer that solubilizes at pH 7. Developed microparticles were characterized for different parameters and the formulation showing the highest drug entrapment was selected for photodegradation studies. Photodegradation studies were performed in solar light and in UV light at 254 nm and 366 nm for 7 days. The concentration of drug was determined spectrophotometrically at 290 nm. The percent degradation under solar light for pure drug was 25% and no significant degradation was seen in drug-loaded microparticles. Degradation under UV radiation 254 nm and 366 nm was found to be 38.6% and 12.11% and 35.11% and 6.13% for pure drug and drug-loaded microparticles, respectively. Microencapsulation decreases the penetration as well as absorption of radiation, which enhances the protection of pantoprazole sodium.
Assuntos
Composição de Medicamentos , Tamanho da Partícula , Microscopia Eletrônica de Varredura , Polímeros/química , Inibidores da Bomba de Prótons , Solubilidade , SolventesAssuntos
Adenocarcinoma/secundário , Radioisótopos de Flúor , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Fluoreto de Sódio , Neoplasias da Coluna Vertebral/secundário , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Anilidas/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Precoce , Reações Falso-Negativas , Fluordesoxiglucose F18 , Humanos , Leuprolida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Osteosclerose/diagnóstico por imagem , Osteosclerose/etiologia , Prostatectomia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/tratamento farmacológico , Neoplasias da Coluna Vertebral/radioterapia , Medronato de Tecnécio Tc 99m , Compostos de Tosil/administração & dosagemRESUMO
Squamous cell carcinoma especially of oral cavity is one of the most prevalent diseases in the world. Chromosomal rearrangements are known to play important role in the pathogenesis of many diseases including cancer. In case of Head and Neck Squamous Cell Carcinoma, chromosomal changes are detectable at all stages of tumor development providing excellent opportunity for chromosomal prognosis and therapy. The present work aimed to study the frequency and pattern of chromosomal aberrations in human peripheral blood lymphocyte culture of freshly diagnosed Head and Neck squamous cell carcinoma patients. Further In vitro anticancer drugs (5-Fluorouracil {5-FU } and Cisplatin) effects were studied for clastogenicity. Results indicated significant impact of chemotherapeutic agents on the frequency of different types of chromosomal rearrangements.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/genética , Aberrações Cromossômicas/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/genética , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Estudos de Casos e Controles , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Células Tumorais CultivadasRESUMO
Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Doenças da Unha/tratamento farmacológico , Unhas/efeitos dos fármacos , Administração Tópica , Química Farmacêutica/métodos , Humanos , Doenças da Unha/metabolismo , Unhas/metabolismo , PermeabilidadeRESUMO
OBJECTIVE: A cross-sectional institutional-based study was undertaken to know the prevalence of Gestational Diabetes Mellitus (GDM) among Indian pregnant women. SUBJECTS AND METHODS: 325 pregnant women were screened for evidence of diabetes who were previously not known to be diabetic. They underwent 75 g, 2 hour, oral glucose tolerance test (OGTT). Chi-square test was done for statistically association of variables in GDM. RESULTS AND CONCLUSIONS: The results of this study indicate that bad obstetrics history, obese patient on high calorie diet especially non vegetarian diet with less physical activity are highly prone to develop GDM.
Assuntos
Diabetes Gestacional/epidemiologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Estudos Transversais , Diabetes Gestacional/genética , Feminino , Humanos , Índia/epidemiologia , Insulina/metabolismo , Resistência à Insulina , Pessoa de Meia-Idade , Atividade Motora , Gravidez , População Urbana , Adulto JovemRESUMO
The aim of the present study was to determine whether systemic sensitisation and chronic aeroallergen challenge in macaques replicate the classical and emerging immunology and molecular pathology of human asthma. Macaques were immunised and periodically challenged over 2 yrs with house dust mite allergen. At key time-points, serum, bronchoalveolar lavage (BAL) and bronchial biopsies were assayed for genes, proteins and lymphocyte subpopulations relevant to clinical asthma. Immunisation and periodic airway challenge induced changes in immunoglobulin E, airway physiology and eosinophilia consistent with chronic, dual-phase asthma. Sensitisation increased interleukin (IL)-1ß and -6 concentrations in serum, and IL-13 expression in BAL cells. Airway challenge increased: early expression of IL-5, -6, -13 and -19, and eotaxin; and variable late-phase expression of IL-4, -5 and -13, and thymus- and activation-regulated chemokine in BAL cells. CD4+ lymphocytes comprised 30% of the CD3+ cells in BAL, increasing to 50% in the late phase. Natural killer T-cells represented <3% of the CD3+ cells. Corticosteroid treatment reduced serum histamine levels, percentage of CD4+ cells and monocyte-derived chemokine expression, while increasing CD3+ and CD8+ cells in BAL. Sensitisation and periodic aeroallergen challenge of cynomolgus macaques results in physiological, cellular, molecular and protein phenotypes, and therapeutic responses observed in human asthma, providing a model system useful in target and biomarker discovery, and translational asthma research.
Assuntos
Corticosteroides/farmacologia , Asma/patologia , Alérgenos , Animais , Biomarcadores/metabolismo , Lavagem Broncoalveolar , Modelos Animais de Doenças , Citometria de Fluxo/métodos , Regulação da Expressão Gênica , Humanos , Imunoglobulina E/metabolismo , Células Matadoras Naturais/citologia , Pulmão/fisiologia , Linfócitos/citologia , Macaca , Ácaros , EsteroidesRESUMO
CD44 is a glycosylated adhesion molecule and osteopontin is one of its ligand. CD44 undergoes alternative splicing to produce variant isoforms. Our recent studies have shown an increase in the surface expression of CD44 isoforms (sCD44 and v4-v10 variant CD44) in prostate cancer cells over-expressing osteopontin (PC3/OPN). Formation of CD44/MMP9 complex on the cell surface is indispensable for MMP9 activity. In this study, we have characterized the expression of variant CD44 using RT-PCR, surface labeling with NHS-biotin, and immunoblotting. Expression of variant CD44 encompassing v4-v10 and sCD44 at mRNA and protein levels are of the same levels in PC3 and PC3/OPN cells. However, an increase in the surface expression of v6, v10, and sCD44 in PC3/OPN cells suggest that OPN may be a ligand for these isoforms. We then proceeded to determine the role of sCD44 in MMP9 activation. Based on our previous studies in osteoclasts, we hypothesized that phosphorylation of CD44 has a role on its surface expression and subsequent activation of MMP9. We have prepared TAT-fused CD44 peptides comprising unphosphorylated and constitutively phosphorylated serine residues at positions Ser323 and Ser325. Transduction of phosphopeptides at Ser323 and Ser323/325 into PC3 cells reduced the surface levels of CD44, MMP9 activity, and cell migration; but had no effect on the membrane localization of MMP9. However, MMP9 knock-down PC3 cells showed reduced CD44 at cellular and surface levels. Thus we conclude that surface expression of CD44 and activation of MMP9 on the cell surface are interdependent.
Assuntos
Membrana Celular/metabolismo , Variação Genética , Receptores de Hialuronatos/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias da Próstata/metabolismo , Sequência de Aminoácidos , Linhagem Celular Tumoral , Membrana Celular/enzimologia , Movimento Celular , Humanos , Receptores de Hialuronatos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Dados de Sequência Molecular , Osteopontina/metabolismo , Fosforilação , Neoplasias da Próstata/enzimologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , TransfecçãoRESUMO
The range of implantable cardiac pacing devices has expanded, with the advances in available technology. Indications for cardiac pacing devices, that is pacemakers, implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy devices (CRTs), have expanded for the treatment, diagnosis and monitoring of bradycardia, tachycardia and heart failure. While the need for pacemakers is increasing, not all patients who require pacemakers are receiving them, especially in the Asia-Pacific region. There is a need to be more critical in advising the use of more expensive devices like ICDs and CRT/CRT-D devices, since most patients in the Asia-Pacific region pay out of pocket for these therapies. The AHA-ACC guidelines need not be blindly followed, since they are too wide-sweeping and are often based on the intention-to-treat basis of trials rather than on the parameters of the patients actually enrolled.
RESUMO
BACKGROUND AND PURPOSE: Drug-induced prolongation of the QT interval can lead to torsade de pointes, a life-threatening ventricular arrhythmia. Finding appropriate assays from among the plethora of options available to predict reliably this serious adverse effect in humans remains a challenging issue for the discovery and development of drugs. The purpose of the present study was to develop and verify a reliable and relatively simple approach for assessing, during preclinical development, the propensity of drugs to prolong the QT interval in humans. EXPERIMENTAL APPROACH: Sixteen marketed drugs from various pharmacological classes with a known incidence -- or lack thereof -- of QT prolongation in humans were examined in hERG (human ether a-go-go-related gene) patch-clamp assay and an anaesthetized guinea-pig assay for QT prolongation using specific protocols. Drug concentrations in perfusates from hERG assays and plasma samples from guinea-pigs were determined using liquid chromatography-mass spectrometry. KEY RESULTS: Various pharmacological agents that inhibit hERG currents prolong the QT interval in anaesthetized guinea-pigs in a manner similar to that seen in humans and at comparable drug exposures. Several compounds not associated with QT prolongation in humans failed to prolong the QT interval in this model. CONCLUSIONS AND IMPLICATIONS: Analysis of hERG inhibitory potency in conjunction with drug exposures and QT interval measurements in anaesthetized guinea-pigs can reliably predict, during preclinical drug development, the risk of human QT prolongation. A strategy is proposed for mitigating the risk of QT prolongation of new chemical entities during early lead optimization.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Síndrome do QT Longo/induzido quimicamente , Animais , Cromatografia Líquida , Desenho de Fármacos , Eletrocardiografia , Canais de Potássio Éter-A-Go-Go/metabolismo , Cobaias , Humanos , Espectrometria de Massas , Modelos Animais , Técnicas de Patch-ClampRESUMO
In vitro iontophoretic delivery of glipizide across the pigskin was investigated. The experiment was carried out at three different donor drug concentrations using cathodal iontophoresis (current density 0.5 mA cm(-2)) with corresponding passive controls. At all concentration levels, iontophoresis showed enhanced permeation rate compared to passive controls (P<0.01). For passive permeation, the steady-state flux significantly increased with the increase in donor drug concentration (P<0.01). Passive process followed zero-order profile while the profile was nonlinear in iontophoresis. Competition by chloride ions released in the cathode compartment could be the reason. Flux enhancement was highest at the lowest drug load and lowest at the highest drug load. The target flux of glipizide was calculated to be 0. 4147 micromol h(-1). As the highest flux obtained was 0.2727 micromol cm(-2) h(-1), it can be said that glipizide is a promising candidate for iontophoretic delivery.
Assuntos
Glipizida/administração & dosagem , Glipizida/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Algoritmos , Animais , Soluções Tampão , Cloretos/metabolismo , Cromatografia Líquida de Alta Pressão , Difusão , Técnicas In Vitro , Iontoforese , Membranas/efeitos dos fármacos , Membranas/metabolismo , Octanóis/química , Veículos Farmacêuticos , Solubilidade , Soluções , Espectrofotometria Ultravioleta , SuínosRESUMO
A 3(2) factorial design was employed to produce controlled release solid dispersions of diclofenac sodium in Eudragit RS and RL by coevaporation of their ethanol solution in a flash evaporator. The effect of critical formulation variables namely total polymer pay loads and levels of Eudragit RL on percent drug incorporation (% DI), drug release at the end of 12 hours (Rel(12)) and drug release at the end of 3 hours (Rel(3)) were analyzed using response surface methodology. The parameters were evaluated using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables studied exerted a significant influence (p < 0.05) on the drug release whereas the total polymer levels emerged as a lone factor significantly influencing the percent drug incorporation. Numerical optimization technique employing desirability approach was used to develop a new formulation by setting constraints on the dependent and independent variables. The experimental values of % DI, Rel(12) and Rel(3) for the optimized batch were found to be 95.22 +/- 1.13%, 74.52 +/- 3.16% and 29.37 +/- 1.26% respectively which were in close agreement with those predicted by the mathematical models. The Fourier transform infrared spectroscopy, Differential scanning calorimetry and Powder x-ray diffractometry confirmed that the drug was reduced to molecular or microcrystalline form in the hydrophobic polymeric matrices, which could be responsible for the controlled drug release from the solid dispersions. The drug release from the solid dispersions followed first order rate kinetics and was characterized by Higuchian diffusion model.
RESUMO
A central composite design was employed to produce microcapsules of propranolol hydrochloride by o/o emulsion solvent evaporation technique using a mixture of cellulose acetate butyrate as coat material and span-80 as an emulsifier. The effect of formulation variables namely levels of cellulose acetate butyrate (X(1)) and percentage of Span-80 (X(2)) on encapsulation efficiency (Y(1)), drug release at the end of 1.5 h (Y(2)), 4 h (Y(3)), 8 h (Y(4)), 14 h (Y(5)), and 24 h (Y(6)) were evaluated using the F test. Mathematical models containing only the significant terms were generated for each response parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables exerted a significant influence (P <0.05) on Y(1) whereas the cellulose acetate butyrate level emerged as the lone factor which significantly influenced the other response parameters. Numerical optimization using desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of Y(1), Y(2), Y(3), Y(4), Y(5), and Y(6) for the optimized formulation was found to be 92.86+/-1.56% w/w, 29.58+/-1.22%, 48.56+/-2.56%, 60.85+/-2.35%, 76.23+/-3.16% and 95.12+/-2.41%, respectively which were in close agreement with those predicted by the mathematical models. The drug release from microcapsules followed first order kinetics and was characterized by Higuchi diffusion model. The optimized microcapsule formulation developed was found to comply with the USP drug release test-1 for extended release propranolol hydrochloride capsules.
RESUMO
Glipizide was complexed with beta-cyclodextrin in an attempt to enhance the drug solubility. The phase solubility diagram was classified as A(L) type, which was characterized by an apparent 1:1 stability constant that had a value of 413.82 M(-1). Fourier transform infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry and proton nuclear magnetic resonance spectral analysis indicated considerable interaction between the drug and beta-cyclodextrin. A 2(3) factorial design was employed to prepare hydroxypropyl methylcellulose (HPMC) matrix tablets containing the drug or its complex. The effect of the total polymer loads (X1), levels of HPMC K100LV (X9), and complexation (X3) on release at first hour (Y1), 24 h (Y2), time taken for 50% release (Y3), and diffusion exponent (Y4) was systematically analyzed using the F test. Mathematical models containing only the significant terms (P < 0.05) were generated for each parameter by multiple linear regression analysis and analysis of variance. Complexation was found to exert a significant effect on Y1, Y2, and Y3, whereas total polymer loads significantly influenced all the responses. The models generated were validated by developing two new formulations with a combination of factors within the experimental domain. The experimental values of the response parameters were in close agreement with the predicted values, thereby proving-the validity of the generated mathematical models.
Assuntos
Glipizida/administração & dosagem , Hipoglicemiantes/administração & dosagem , beta-Ciclodextrinas/química , Varredura Diferencial de Calorimetria , Excipientes , Glipizida/química , Hipoglicemiantes/química , Derivados da Hipromelose , Espectroscopia de Ressonância Magnética , Metilcelulose/análogos & derivados , Microscopia Eletrônica de Varredura , Solubilidade , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos , Difração de Raios XRESUMO
This study aimed to evaluate whether patients with advanced non-small-cell lung cancer experience disrupted rest-activity daily rhythms, poor sleep quality, weakness, and maintain attributes that are linked to circadian function such as fatigue. This report describes the rest-activity patterns of 33 non-small-cell lung cancer patients who participated in a randomised clinical trial evaluating the benefits of melatonin. Data are reported on circadian function, health-related quality of life (QoL), subjective sleep quality, and anxiety/depression levels prior to randomisation and treatment. Actigraphy data, an objective measure of circadian function, demonstrated that patients' rest-activity circadian function differs significantly from control subjects. Our patients reported poor sleep quality and high levels of fatigue. Ferrans and Powers QoL Index instrument found a high level of dissatisfaction with health-related QoL. Data from the European Organization for Research and Treatment for Cancer reported poor capacity to fulfil the activities of daily living. Patients studied in the hospital during or near chemotherapy had significantly more abnormal circadian function than those studied in the ambulatory setting. Our data indicate that measurement of circadian sleep/activity dynamics should be accomplished in the outpatient/home setting for a minimum of 4-7 circadian cycles to assure that they are most representative of the patients' true condition. We conclude that the daily sleep/activity patterns of patients with advanced lung cancer are disturbed. These are accompanied by marked disruption of QoL and function. These data argue for investigating how much of this poor functioning and QoL are actually caused by this circadian disruption, and, whether behavioural, light-based, and or pharmacologic strategies to correct the circadian/sleep activity patterns can improve function and QoL.