Self-microemulsifying Drug Delivery System for Solubility and Bioavailability Enhancement of Eprosartan Mesylate: Preparation, In-vitro, and In-vivo Evaluation.

BACKGROUND: Formulations of eprosartan mesylate with a surfactant, like Kolliphor HS 15, an oil phase like Labrafil M 1944 CS, and a cosurfactant Transcutol HP by employing a liquid self-microemulsifying drug delivery system (SMEDDS) after screening several vehicles have been studied. OBJECTIVE: This study aimed to prepare a liquid self-microemulsifying drug delivery system for increasing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate. METHODS: The micro-emulsion unit, achieved through the phase diagram and augmented with the central-composite design (CCD) surface response process, was adjusted into SMEDDS by lyophilization using sucrose as a cryoprotective agent. Particle size, self-emulsification time, polydispersion index (PDI), zeta potential, differential scanning calorimeter (DSC) screening, in-vitro drug release, and in-vivo pharmacokinetics were the essential features of the formulations. The subsequent DSC experimentation indicated that the drug was integrated into S-SMEDDS. Eprosartan mesylate loaded SMEDDS formulation showed greater in-vitro and in-vivo drug release than conventional solid doses. RESULTS: SMEDDS has reported effectiveness in reducing the impact of pH of eprosartan mesylate, thereby improving its release efficiency. The HPLC method was successfully implemented to assess eprosartan mesylate concentration in Wister rat plasma after oral administration of commercial tablet EM, SMEDDS, and eprosartan mesylate. The pharmacokinetics parameters for rats were Cmax 1064.91 ± 225 and 1856.22 ± 749 ngmL-1, Tmax 1.9 ± 0.3 hr, and 1.2 ± 0.4 hr and AUC0~t were 5314.36 ± 322.61 and 7760.09 ± 249 ng/ml hr for marketed tablets and prepared SSMEDDS, respectively. When determined by AUC0~1, the relative bioavailability of eprosartan mesylate S-SMEDDC was 152.09 ± 14.33%. CONCLUSION: The present study reports the formulation of a self-microemulsifying drug delivery system for enhancing the solubility and bioavailability of a poorly water-soluble eprosartan mesylate in an appropriate solid dosage form.

Modeling nonlinear fractional-order subdiffusive dynamics in nuclear reactor with artificial neural networks.

This paper presents the development and analysis of artificial neural network (ANN) models for the nonlinear fractional-order (FO) point reactor kinetics model, FO Nordheim-Fuchs model, inverse FO point reactor kinetics model and FO constant delayed neutron production rate approximation model. These models represent the dynamics of a nuclear reactor with neutron transport modeled as subdiffusion. These FO models are nonlinear in nature, are comprised of a system of coupled fractional differential equations and integral equations, and are considered to be difficult for solving both analytically and numerically. The ANN models were developed using the data generated from these models. The work involves the iterative process of ANN learning with different combinations of layers and neurons. It is shown through extensive simulation studies that the developed ANN models faithfully capture the transient and steady-state dynamics of these FO models, thereby providing a satisfactory representation for the nonlinear subdiffusive process of neutron transport in a nuclear reactor.

Role of Conjunctival Ultraviolet Autofluorescence in Ocular Surface Squamous Neoplasia.

OBJECTIVE: To evaluate the adjunctive role of conjunctival autofluorescence in the management of ocular surface squamous neoplasia (OSSN). MATERIALS AND METHODS: Seventeen patients with clinically diagnosed OSSN were included. Morphological characteristics, type of OSSN, and autofluorescence photographs of the lesion were captured. Presence and area of conjunctival ultraviolet autofluorescence (CUVAF) were the main outcome measures. RESULTS: Overall, 17 patients with 15 (88%) primary and 2 (12%) recurrent OSSN were included. Common locations were temporal (n = 10), nasal (n = 5), and diffuse variety (n = 2). Morphologically, there were 4 (22.2%) nodular, 4 (22.2%) leucoplakic, 3 (16.7%) gelatinous, and 1 (5.5%) each of papillary, nodulo-ulcerative, and diffuse variety. Mixed morphology was present in 4 eyes (22.2%). Sixteen of 18 eyes (88.9%) with OSSN displayed autofluorescence on CUVAF images. The mean area of CUVAF was 15.82 mm2 (10.77-19.59 mm2). Autofluorescence was reported in 8 eyes (44.4%) which had negative reports on impression cytology. CONCLUSIONS: Conjunctival autofluorescence was seen in the majority of cases with OSSN, in spite of negative cytology reports. Our study demonstrates that CUVAF may serve as an effective ancillary, non-invasive, and resource-friendly tool for supplementing the clinical diagnosis of OSSN, especially in diffuse and recurrent lesions that are not amenable to surgical intervention.

Perceived difficulties and complications in learners of phacoemulsification: A principal component analysis model.

PURPOSE: To evaluate the difficulty perceived of each step of phacoemulsification and analyze the factors affecting them. METHODS: Overall, 12 trainee residents were allotted 10 cases of phacoemulsification of eyes with senile cataract, under a single observer, and the steps of each surgery were rated from very easy to very difficult with a questionnaire. The completion rates of steps and complications of each surgery were noted. Principal component analysis of the responses to the difficulty level questionnaire was conducted to obtain factors resulting in the perceived difficulty. RESULTS: The lowest difficulty scores were for initial step of incision creation (1.63 ± 0.84), followed by intraocular lens insertion (2.51 ± 0.8). The most difficult step was divide/chop of the nucleus (3.74 ± 0.97) followed by phacoemulsification (3.32 ± 0.82). Highest completion rates were seen for the initial steps of the surgery and the lowest for divide/chop. We identified two major patterns of difficulty among the trainees - one for steps involving high amount of binocularity and the other, for steps involving high precision of hand control. The rate of complication of our study was within acceptable range. CONCLUSION: Although trainees have practiced phacoemulsification steps on simulation, real-life situation may bring in unprecedented level of difficulty and challenges, which may be documented and used for targeted improvement of surgical skills. Stereopsis and hand control training should form a major part of training modules of cataract surgery both on simulation and real-life scenarios.

Pythium Keratitis Leading to Fatal Cavernous Sinus Thrombophlebitis.

PURPOSE: To report a case of Pythium insidiosum keratitis leading to fatal cavernous sinus thrombophlebitis. METHODS: Case report. RESULTS: A 70-year-old man presented with excruciating pain, redness, and diminution of vision in his left eye for 2 weeks after washing his hair with tap water. A total corneal ulcer with surrounding infiltrates and associated corneal thinning was present. Corneal scraping revealed the presence of Gram-positive cocci. KOH wet mount and in vivo confocal microscopy revealed branching hyphae. Combined antibacterial and antifungal treatment was started, but 4 days later, the ulcer showed signs of worsening with perforation for which a large therapeutic penetrating keratoplasty was done. The host cornea showed branching septate hyphae on Sabarouds Dextrose Agar. Two weeks later, the patient developed left eye proptosis with associated extraocular movement restriction. Magnetic resonance imaging of the head and orbit revealed cavernous sinus thrombophlebitis. Lid sparing partial exenteration was performed. Polymerase chain reaction revealed P. insidiosum. The patient subsequently developed a cerebrovascular attack and died of its complications. CONCLUSIONS: Ocular pythiosis may lead to cavernous sinus thrombophlebitis and can even be life threatening. Timely diagnosis and early radical surgery are of value. A high index of suspicion must be kept for P. insidiosum in cases with suspected fungal etiology not responding to conventional treatment.

Triple chamber: a clinical rarity after deep anterior lamellar keratoplasty and role of optical coherence tomography in management.

PURPOSE: To report a case demonstrating triple chamber following deep anterior lamellar keratoplasty (DALK) and its successful intra-operative optical coherence tomography-guided management. METHOD: Case report of a young male with macular corneal dystrophy, who underwent DALK in his left eye by Big-Bubble technique. The surgery was uneventful. On the first post-operative day, triple chamber was observed and followed-up with serial clinical photography and anterior segment optical coherence tomography. Due to decrease in graft clarity and increase in volume of the two extra chambers, interface drainage along with descemetopexy was undertaken 4 days later. RESULT: The compartments constituting the triple chamber were those in-between the donor tissue and host pre-Descemet layer (Dua's layer), the latter and host Descemet membrane and the true anterior chamber. Presence of viscoelastic in the interface was identified as the cause. Microscope integrated optical coherence tomography (MiOCT) guided drainage followed by intracameral air tamponade ensured near total disappearance of the two extra chambers at the end of surgery. Examination on the next day confirmed complete apposition of the graft and host. CONCLUSION: To the best of our knowledge, this is a unique demonstration of Dua's layer in vivo by slit lamp biomicroscopy and description of MiOCT guided management of triple chamber.

Metastatic renal cell carcinoma presenting as one-and-a-half syndrome.

We report a case of 43-year-old male, presented with sudden onset binocular diplopia on lateral gazes. Ocular examination showed features of ipsilateral one-and-a-half syndrome. Comprehensive systemic work in conjunction with magnetic resonance imaging of the brain illustrated irregular mixed solid and cystic lesions in the brainstem, possibly indicative of brain metastases. Further imaging revealed hidden renal cell carcinoma as a primary neoplasm, which led to secondary manifestations.

Descemet stripping automated endothelial keratoplasty.

Endothelial keratoplasty is at present the gold standard for surgical treatment of corneal endothelial pathologies not associated with significant corneal scar. Tremendous progress has been made in recent years in improving the technology of endothelial keratoplasty techniques, such as descemet stripping automated endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty. In this review, we discuss the current techniques and outcomes of DSAEK.

A new and simple method to construct root locus of general fractional-order systems.

Recently fractional-order (FO) differential equations are widely used in the areas of modeling and control. They are multivalued in nature hence their stability is defined using Riemann surfaces. The stability analysis of FO linear systems using the technique of Root Locus is the main focus of this paper. Procedure to plot root locus of FO systems in s-plane has been proposed by many authors, which are complicated, and analysis using these methods is also difficult and incomplete. In this paper, we have proposed a simple method of plotting root locus of FO systems. In the proposed method, the FO system is transformed into its integer-order counterpart and then root locus of this transformed system is plotted. It is shown with the help of examples that the root locus of this transformed system (which is obviously very easy to plot) has exactly the same shape and structure as the root locus of the original FO system. So stability of the FO system can be directly deduced and analyzed from the root locus of the transformed IO system. This proposed procedure of developing and analyzing the root locus of FO systems is much easier and straightforward than the existing methods suggested in the literature. This root locus plot is used to comment about the stability of FO system. It also gives the range for the amplifier gain k required to maintain this stability. The reliability of the method is verified with analytical calculations.