Canagliflozin loaded SMEDDS: formulation optimization for improved solubility, permeability and pharmacokinetic performance

Neena Bedi,Dilpreet Singh,Ashok K. Tiwary 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.1

The aim of the present investigation is to systematically optimize and develop microemulsion preconcentrates to improve the solubility and oral bioavailability profile of canagliflozin employing D-optimal mixture design. Preconcentrate constituents, i.e. oils, surfactants and co-surfactants were selected on the basis of solubility studies and their concentration range capable of influencing the formation of microemulsions was determined. D-optimal mixture design was employed for studying the interaction behavior of desired responses and optimized using desirability approach. The optimized formulation was evaluated for its in vitro, ex vivo and in vivo behavior to determine the dissolution rate, permeation rate and oral bioavailability of the drug. The optimized formulation containing Lauroglycol FCC (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) showed desired attributes of measured responses with minimum experimental variation and desirability value of 0.751. The morphological behavior showed uniform nano-structured globules with negligible aggregation as confirmed in transmission electron microscopy. Ex vivo permeation rate of the drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.51, 5.62, 4.52 and 2.98 folds higher, respectively, as compared to drug powder and marketed tablets Compared with the pure drug and commercial tablets, enhanced in vitro dissolution rate of optimized formulation was observed, resulting in 2.56 fold enhancement in Cmax and AUC 0–24h following oral administration in fasting wistar rats. Establishment of level A IVIVC for the developed SMEDDS indicated excellent goodness of fit between the in vitro drug release and in vivo drug absorbed. Accelerated stability studies indicated stability of the optimized formulation over 3 months storage.

Predictability of the Madden-Julian Oscillation in the Intraseasonal Variability Hindcast Experiment (ISVHE)

Neena, J.M.,Lee, J.Y.,Waliser, D.,Wang, B.,Jiang, X. AMERICAN METEOROLOGICAL SOCIETY 2014 Journal of climate Vol.27 No.12

The Madden-Julian oscillation (MJO) represents a primary source of predictability on the intraseasonal time scales and its influence extends from seasonal variations to weather and extreme events. While the last decade has witnessed marked improvement in dynamical MJO prediction, an updated estimate of MJO predictability from a contemporary suite of dynamic models, in conjunction with an estimate of their corresponding prediction skill, is crucial for guiding future research and development priorities. In this study, the predictability of the boreal winter MJO is revisited based on the Intraseasonal Variability Hindcast Experiment (ISVHE), a set of dedicated extended-range hindcasts from eight different coupled models. Two estimates of MJO predictability are made, based on single-member and ensemble-mean hindcasts, giving values of 20-30 days and 35-45 days, respectively. Exploring the dependence of predictability on the phase of MJO during hindcast initiation reveals a slightly higher predictability for hindcasts initiated from MJO phases 2, 3, 6, or 7 in three of the models with higher prediction skill. The estimated predictability of MJO initiated in phases 2 and 3 (i.e., convection in Indian Ocean with subsequent propagation across Maritime Continent) being equal to or higher than other MJO phases implies that the so-called Maritime Continent prediction barrier may not actually be an intrinsic predictability limitation. For most of the models, the skill for single-member (ensemble mean) hindcasts is less than the estimated predictability limit by about 5-10 days (15-25 days), implying that significantly more skillful MJO forecasts can be afforded through further improvements of dynamical models and ensemble prediction systems (EPS).

Synthesis and characterization of α-mangostin imprinted polymers and its application for solid phase extraction

Zakia, Neena,Zulfikar, Muhammad A.,Amran, Muhammad B. Techno-Press 2020 Advances in materials research Vol.9 No.4

α-mangostin imprinted polymers have been synthesized by a non-covalent imprinting approach with α-mangostin as a template molecule. The α-mangostin molecularly imprinted polymers (MIPs) prepared by radical polymerization using methacrylic acid, ethlylene glycol dimethacrylate, benzoyl peroxide, and acetonitrile, as a monomer, crosslinker, initiator, and porogen, respectively. The template was removed by using methanol:acetic acid 90:10 (v/v). The physical characteristics of the polymers were investigated by Fourier Transform Infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The rebinding studies were carried out by batch methods. The results exhibited that the MIPs was able to adsorb the α-mangostin at pH 2 and the contact time of 180 min. The kinetic adsorption data of α-mangostin performed the pseudo-second order model and followed the Langmuir isotherm model with the adsorption capacity of 16.19 mg·g-1. MIPs applied as a sorbent material in solid-phase extraction, namely molecularly imprinted solid-phase extraction (MISPE) and it shows the ability for enrichment and clean-up of α-mangostin from the complex matrix in medicinal herbal product and crude extract of mangosteen (Garcinia mangostana L.) pericarp. Both samples, respectively, which were spiked with α-mangostin gives recovery more than 90% after through by MISPE in all concentration ranges.

Association Rule Mining : A Survey

Jagmeet Kaur,Neena Madan 보안공학연구지원센터 2015 International Journal of Hybrid Information Techno Vol.8 No.7

Last few years have seen a rapid growth in the area of data mining. Association rule mining is one of the most important techniques of data mining. It is a technique which is used to discover the frequently occurring patterns in the database. A lot of research has been done in the area of association rule mining. This paper gives a brief overview of association rule mining, some of its applications and algorithms. The limit of discussion is to the areas where association rule is used to a high extent.

Three Rare Concurrent Complications of Tertiary Hyperparathyroidism: Maxillary Brown Tumor, Uremic Leontiasis Ossea, and Hungry Bone Syndrome

Natalie Bransky,Neena Ramesh Iyer,Sophie Mestman Cannon,Alexander Hanlin Tyan,Praneet Mylavarapu,Ryan Orosco,David Brain Hom,Alan Ali Moazzam 대한골대사학회 2020 대한골대사학회지 Vol.27 No.3

A 48-year-old woman in her 40’s with end-stage renal disease and tertiary hyperparathyroidism (HPT) presented for a rapidly progressive maxillary tumor. Initial workup was notable for elevated intact parathyroid hormone (PTH) and diffuse thickening of skull and facial bones on computed tomography, and maxillary tumor biopsy with multinucleated giant cells. She underwent subtotal parathyroidectomy (with removal of a parathyroid adenoma and 2 hyperplastic glands) and partial resection of maxillary brown tumor. The patient’s post-operative course was complicated by hungry bone syndrome, with hypocalcemia refractory to aggressive calcium repletion. Teriparatide (recombinant PTH) was utilized with rapid resolution of hypocalcemia. To our knowledge, this is the first case of maxillary brown tumor in tertiary HPT to be reported in the USA. This case also supports teriparatide as a novel therapeutic for hungry bone syndrome refractory to aggressive calcium repletion.

Enhancing solubility of poorly aqueous soluble drugs: critical appraisal of techniques

Dilpreet Singh,Neena Bedi,Ashok K. Tiwary 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.5

A wide variety of new medication disclosures launched by specific benefits of the general public are laced with poor aqueous solubility problems that often obstruct their bioavailability and formulation development. Literature survey demonstrates that about 70% of active pharmaceutical ingredients and new chemical entities are considered as poorly soluble. Numerous formulation strategies and methodologies are accessible in literature like SMEDDS, micro/ nanoparticles, liposomes, solid dispersions and co-crystals that have been broadly examined for enhancing the solubility of poorly water soluble drugs. The pharmaceutical techniques that are used for preparing these dosage forms play a crucial role in the overall formulation development and scalability. Hence, it seems highly essential to recognize various equipments and the importance of their critical processing parameters while using them to tailor specific product characteristics in the dosage forms. Providing a comprehensive overview, this review endeavors to provide important pharmaceutical techniques used for formulating various dosage forms for solubility enhancement of poorly water soluble drugs.

An Uncommon Side Effect of a Commonly Used Antibiotic: Amoxicillin-Clavulanic Acid Induced Hepatitis

Vinay Mathew Thomas,Neena Thomas-Eapen 대한가정의학회 2017 Korean Journal of Family Medicine Vol.38 No.5

Amoxicillin-Clavulanic acid continues to be one of the most commonly used antibiotic combinations. Hepatic in-jury due to this antibiotic is rare. We report a case of amoxicillin-clavulanic acid induced hepatitis causing painless jaundice to bring to attention this rare side effect of this commonly used antibiotic. This is a case of a 62-year-old Caucasian female, who presented with acute onset severe painless jaundice, nausea, vomiting, and pruritus of less than 1-week duration. She had completed a course of amoxicillin-clavulanic acid 3 weeks prior to presentation. A careful history pointed to this simple diagnosis. It may be easily missed without an in-depth history and the patient may be subjected to unnecessary expensive tests. This case is reported to highlight cost conscious care by keeping in mind a rare side effect of the commonly used antibiotic.

Starvation and Desiccation Tolerance in Indian Populations of Drosophila Melanogaster

Ravi Parkash,Shamina,Neena 한국유전학회 1993 Genes & Genomics Vol.15 No.3

Data on mean survival times for starvation tolerance under highly wet conditions and desiccation tolerance at zero percent humidity revealed significant differences for four Indian geographical populations of D.melanogaster. The genetic control of these physiological traits was ascertained from the occurrence of little differences between two successive generations of various isofemale lines of D.melanogaster populations. The north Indian populations of D.melanogaster revealed significant higher tolerance for desiccation as compared with the southern populations. On the contrary, for starvation tolerance, under humid conditions, the survival values of the southern populations were found to be significantly higher than that of north Indian populations. It can be argued that the south Indian populations of D.melanogaster which lived in a hot and humid environment throughout the year were poorly protected against desiccation but displayed higher starvation tolerance due to steady metabolic rate at increased ambient temperature. Thus. Indian geographical populations of D.melanogaster revealed adaptively maintained genetic divergence for starvation and desiccation tolerance.

Comparison between lignocaine nebulization and airway nerve block for awake fiberoptic bronchoscopy-guided nasotracheal intubation: a single-blind randomized prospective study

Pooja Rawat Mathur,Neena Jain,Aji Kumar,Beena Thada,Veena Mathur,Deepak Garg 대한마취통증의학회 2018 Korean Journal of Anesthesiology Vol.71 No.2

Background: The preferred management strategy for difficult airways is awake fiberoptic bronchoscopy-guided intubation, which requires effective airway anesthesia to ensure patient comfort and acceptance. This randomized single-blind prospective study was conducted to compare lignocaine nebulization and airway nerve block for airway anesthesia prior to awake fiberoptic bronchoscopy-guided intubation. Methods: Sixty adult patients scheduled for surgical procedures under general anesthesia were randomly allocated to two groups. Group N received jet nebulization (10 ml of 4% lignocaine) and Group B received bilateral superior laryngeal and transtracheal recurrent laryngeal nerve blocks (each with 2 ml of 2% lignocaine) followed by fiberoptic bronchoscopy- guided nasotracheal intubation. All patients received procedural sedation with dexmedetomidine. The intubation time, intubating conditions, vocal cord position, cough severity, and degree of patient satisfaction were recorded. Student’s t test was used to analyze parametric data, while the Mann-Whitney U test was applied to non-parametric data and Fisher’s test to categorical data. P values < 0.05 were considered statistically significant. Results: The time taken for intubation was significantly shorter in Group B [115.2 (14.7) s compared with Group N [214.0 (22.2) s] (P = 0.029). The intubating conditions and degree of patient comfort were better in Group B compared with Group N. Although all patients were successfully intubated, patient satisfaction was higher in Group B. Conclusions: Airway nerve blocks are preferable to lignocaine nebulization as they provide superior-quality airway anesthesia. However, nebulization may be a suitable alternative when a nerve block is not feasible.

Mycobacterial formulation in liposomes showed decreasedexpression of CD95/CD95L and caspase activity in T cellsof leprosy patients

Vandana Bisht,Vineeta Chattree,,Neena Khanna,,D.N. Rao 한국물리학회 2005 Current Applied Physics Vol.5 No.2

Leprosy, a debilitating disease shows manifestations ranging from strong cell mediated immune (CMI) response in tuberculoidform (BT/TT) or weak CMI with immunological anergy in lepromatous form (BL/LL). Repeated stimulation with mycobacterialantigen causes activation induced cell death (apoptosis) or anergy in these patients. Previous studies showed in vitro T cell prolif-eration and increased Th1 response with liposomal (particulate) presentation of mycobacterial antigens with immunomodulators(MDP analog, murabutide and T cell peptide of Trat protein). In the present study, the role of caspases; expression of apoptoticmarkers, CD95 and CD95L in T cells of leprosy patients and the eect of particulate formulations in the reversal of apoptosisin BT/TT and BL/LL patient group was studied. Caspase 8/3 activity was maximum (p<0.01) in BL/LL patients in constitutivestate, which was followed by decreased activity in BT/TT and normal subjects. Caspase 8/3 activity increased signicantly(p<0.05) from constitutive state after 5 days of antigen stimulation (inducible state). Both the antigens were equally potent in induc-ing the apoptosis in leprosy patients. A decreased caspase activity using the particulate formulations of both antigens was observedin BL/LL group. The expression of CD95 and CD95L in T cells of leprosy patients increased signicantly after 5 days of antigenstimulation. However, % expression of apoptotic markers by T cells of BL/LL patients decreased signicantly (p<0.05) when theparticulate formulations were used. To summarize, the particulate formulations of antigens with immunomodulators slowed downthe apoptosis and hence T cell anergy in leprosy by stimulating the cells to proliferate..