Role of berberine nanoformulation in epilepsy: A novel therapeutic strategy.

The aim of the present study was to develop a novel formulation of berberine (BBR) and demonstrate its anti-seizure effect in pentylenetetrazole (PTZ) induced kindling model in rats. Nanoparticles of BBR were formulated using Poly Lactic-co-Glycolic Acid (PLGA) as a polymer. Emulsification and solvent evaporation technique was used. PTZ induced kindling model in male wistar rat was used to demonstrate the anti-seizure effect of nano-BBR. The particle size obtained for the final formulation was 242.8 ± 67.35 nm with a PDI of 0.140 ± 0.01. PLGA encapsulated BBR nanoparticles showed the % encapsulation efficiency of 87.33 ± 2.42 % and % drug loading of 48.47 ± 1.34 %. In-vitro drug release data showed sustained release of nano-BBR as compared to BBR. Kinetic study data showed increase in AUC of nano-BBR (35,429.46 h.ng/ml) as compared to BBR (28,211.07 h.ng/ml). Cmax for nano- BBR (2251.90 ng/ml) is approximately 1.6 times greater than BBR (1505.50 ng/ml). Nano- BBR has shown the significant effect on the seizure score. The PLGA encapsulated berberine nanoparticles were prepared by an innovative simple method and offers excellent potential as an antiepileptic agent.

Preclinical Investigation of Transdermal Route for Enhanced Bio-performance of Duloxetine HCl.

The aim of the study was to develop and optimise drug-in-adhesive (DIA) transdermal patch of duloxetine HCl for enhanced drug delivery. DIA patch so developed reduced the dose and dosing frequency by enhancing bio-performance of the drug. A transdermal DIA patch having Duro-Tak 87-2287 as DIA polymer and Transcutol P as permeation enhancer loaded with 40% drug previously complexed with MeßCD duly characterised (FTIR, DSC, and SEM) was developed for in vivo study. Pharmacokinetic parameters of developed formulation were assessed and compared with oral route of administration. Among various permeation enhancers (PEs), Transcutol P exhibited most enhanced permeation (ER ≈ 1.99) in terms of flux and Q24 compared to control group having. Mean of maximum plasma concentration (Cmax) and area under time-concentration curve (AUC0-72) in Wistar rats (n = 6) for transdermal patch (10 mg/kg) was found to be 70.31 ± 11.2 ng/ml and 2997.29 ± 387.4 ng/ml*h, respectively, and were considerably higher than oral dose of DLX (20 mg/kg and 10 mg/kg). Albeit, T1/2 was higher in case of transdermal delivery, but this was due to sustained behaviour of delivery system. These findings highlight the significance of both inclusion complexation and transdermal delivery of DLX using DIA patch for efficient drug absorption.

Neuroprotective effect of Berberine Nanoparticles Against Seizures in Pentylenetetrazole Induced Kindling Model of Epileptogenesis: Role of Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Mechanisms.

There is an unmet need to develop alternative therapeutic strategies to not only restrain seizures but also to alleviate the underlying pathologies and sequelae. Berberine (BBR), an isoquinoline alkaloid, has shown promising effect in the kindling model of epileptogenesis, but due to the poor oral bioavailability its clinical application is limited. So, the present study was designed to study the neuroprotective effect of BBR nanoparticles (enhanced bioavailability as compared to BBR) against seizures in pentylenetetrazole (PTZ) induced kindling model of epileptogenesis. Kindling model was established in male Wistar rats by intraperitoneal (i.p.) administration of PTZ (30 mg/kg) on every alternate day till the animal became fully kindled or till 6 weeks. Three doses of BBR (50, 100, and 200 mg/kg) and nano-BBR (25, 50, 100 mg/kg) were studied for seizure score, percentage of animal kindled, histopathological score, oxidative stress, inflammation, and apoptosis in PTZ treated rats by conducting cytokines, gene expression and protein expression analysis. BBR nanoparticles showed significant effect on the seizure score and percentage of animal kindled, histopathological score, neurobehavioral parameters (Forced swim test, Rotarod), oxidative (MDA, SOD, GSH, GPx) and inflammatory (IL-1beta, TNF-alpha) parameters, apoptotic parameters (Bax and iNOS), and gene (Nrf2, NQO1, HO1) and protein expression (Nrf2) as compared to both PTZ and BBR. BBR nanoparticles showed neuroprotective effect in PTZ induced kindling model of epileptogenesis and proves to be a promising antiepileptogenic therapy for the patients who are at high risk of developing seizures.

Forging Ahead the Repositioning of Multitargeted Drug Ivermectin.

With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.

Advancements in redox-sensitive micelles as nanotheranostics: A new horizon in cancer management.

World Health Organisation (WHO) delineated cancer as one of the foremost reasons for mortality with 10 million deaths in the year 2020. Early diagnosis and effective drug delivery are of utmost importance in cancer management. The entrapment of both bio-imaging dyes and drugs will open novel avenues in the area of tumor theranostics. Elevated levels of reactive oxygen species (ROS) and glutathione (GSH) are the characteristic features of the tumor microenvironment (TME). Researchers have taken advantage of these specific TME features in recent years to develop micelle-based theranostic nanosystems. This review focuses on the advantages of redox-sensitive micelles (RSMs) and supramolecular self-assemblies for tumor theranostics. Key chemical linkers employed for the tumor-specific release of the cargo have been discussed. In vitro characterisation techniques used for the characterization of RSMs have been deliberated. Potential bottlenecks that may present themselves in the bench-to-bedside translation of this technology and the regulatory considerations have been deliberated.

Pharmaceutical strategies for the treatment of bacterial biofilms in chronic wounds.

Biofilms are sessile communities of microorganisms, mainly bacteria, that grow on biotic and abiotic surfaces. These microorganisms are embedded within an extracellular polymeric substance that provides enhanced protection from antimicrobials. Chronic wounds provide an ideal habitat for biofilm formation. Bacteria can easily attach to wound debris and can infect the wound due to an impaired host immune response. This review highlights the mechanism of biofilm formation and the role of biofilms in the pathophysiology of chronic wounds. Our major focus is on various formulation strategies and delivery systems that are employed to eradicate or disperse biofilms, thereby effectively managing acute and chronic wounds. We also discuss clinical research that has studied or is studying the treatment of biofilm-infected chronic wounds.

Transdermal delivery of duloxetine-sulfobutylether-ß-cyclodextrin complex for effective management of depression.

Aim of the study was to reduce the dose and dosing frequency of duloxetine HCl (DXT) by complexation with sulfobutylether-ß-cyclodextrin (SBEßCD), an anionic cyclodextrin through permeation enhancement for more effective management of depression. Spray dried inclusion complexes of drug with SBEßCD were prepared and incorporated in medicated patches followed by their ex vivo permeation and skin retention studies. Then, in vivo efficacy and absorption of the drug from developed optimised patch was determined in Wistar rats by administering drug through oral route (free drug) and transdermal route (complexed drug). Swimming, immobility and climbing parameters in FST while ambulation and rearings parameters in LAT test were assessed. Addition of permeation enhancer (PE) increased drug permeation and the enhancement ratio (ER) was 3.05 and 1.67 for the patch having complexed DXT and spray dried sample of DXT in comparison to free DXT respectively. The amount of drug retained in skin and in optimized medicated patch after 72 h was relatively lower compared to the formulation having free DXT. Enhanced antidepressive activity was observed for complexed drug compared to free drug. We believe that spray dried complexation based transdermal patch can serve as potential innovative drug delivery system for DXT.

Long Acting Polycaprolactone Based Parenteral Formulation of Aripiprazole Targeting Behavioural and Biochemical Deficit in Schizophrenia.

Schizophrenia is a neurodevelopmental disorder which is expressed in the form of disturbed behaviour and abnormal mental functions. Patient's non-adherence to the medicine is the main cause of failure of drug therapy and increases incidence of relapses. Thus, for successful management of disease long acting parenteral formulations were developed. Aripiprazole was encapsulated in biocompatible polycaprolactone microsphere by o/w emulsion solvent-evaporation method in order to achieve sustained release of the drug for several weeks after single subcutaneous administration. They were optimised on the basis of various parameters such as physical appearance, particle size (49.4 µm-387.1 µm), encapsulation efficiency (70%-95%), percentage yield (33%-75%) and drug loading (25.9%-47.5%). The surface topography and sphericity of the microspheres was determined by scanning electron microscopy which revealed that the microspheres formed were spherical and non-porous in nature. The in vitro releases from the selected formulations were found to be 87% and 95% respectively after 45 days of dissolution. In vivo efficacy of optimised formulation showed significantly (p < 0.05) amelioration of various positive, negative and cognitive symptoms associated with schizophrenia and oxidative stress markers in ketamine-induced schizophrenia model in rats for 30 days.

Development of mirtazapine loaded solid lipid nanoparticles for topical delivery: Optimization, characterization and cytotoxicity evaluation.

Mirtazapine, an antidepressant drug has been proved to exert antipruritic effect upon oral administration in numerous clinical trial studies. The objective of the current study was to develop mirtazapine loaded solid lipid nanoparticles (SLNs) and evaluate its potential as a topical drug delivery system for management of pruritus. Mirtazapine loaded SLNs were successfully developed and optimized applying Box-Behnken design. The optimized mirtazapine loaded SLNs were characterized for physicochemical parameters and morphology. The in vitro cytotoxicity and cellular uptake studies of optimized SLNs were performed in human epithelial A-431 cell line. Further, the optimized mirtazapine loaded SLNs dispersion was incorporated into gel and characterized for rheology and texture analysis. The particle size and PDI of optimized mirtazapine loaded was found to be 180.3 nm and 0.209 respectively. The cytotoxicity studies revealed the safety of mirtazapine loaded SLNs on topical administration. The developed gel showed pseudoplastic flow behavior and good textural profile. The in vitro drug release studies showed that the developed mirtazapine loaded SLNs dispersion and its gel followed Korsmeyer-Peppas model (R2 = 0.905) and Higuchi model (R2 = 0.928) respectively. The ex vivo drug permeation studies showed higher values for mean cumulative amount of drug released (548.25 ± 29.29 µg/cm2), permeation flux (45.10 ± 0.78 µg/cm2/h) and skin retention (11.33 ± 0.85%) of SLNs gel in comparison to pure drug gel. The stability studies indicate the stability of SLNs gel for three months at refrigerated and ambient temperatures. Therefore, abovementioned findings suggest that mirtazapine loaded SLNs could be a potential system for topical management of pruritus.

Impact of cyclodextrin derivatives on systemic release of duloxetine HCl via buccal route.

Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of ß-cyclodextrin, i.e. hydroxypropyl-ß-cyclodextrin (HPßCD) and sulfobutylether-ß-cyclodextrin (SBEßCD) and to investigate enhanced cellular uptake of inclusion complexed drug.Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (-1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation.Results: SBEßCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPßCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M-1) for DXT-SBEßCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPßCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug .Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo.

Development of Chitosan-Based Hydrogel Containing Antibiofilm Agents for the Treatment of Staphylococcus aureus-Infected Burn Wound in Mice.

Methicillin-resistant Staphylococcus aureus (MRSA) is considered a common colonizer of burn wound and accounts for high morbidity and mortality all across the globe. Systemic antibiotic therapy which is generally prescribed for these patients has a number of limitations. These include high drug dose, toxicity, and chances of development of drug resistance. However, local delivery of drug not only addresses these limitations but also provides better efficacy at the site of infection. In the present study, hydrogel preparations were developed for the topical delivery of moxifloxacin for the treatment of S. aureus-infected burn wound. Moxifloxacin was characterized by UV, FTIR, DSC, hot-stage microscopy, NMR, and HPLC and loaded into conventional and Boswellia-containing novel gels. Gels were characterized by visual examination, pH, UV spectroscopy, and release assays. In vivo studies showed that both gels were effective in eradicating the bacteria completely from the wound site when treatment was started during the early stage of infection. On the contrary, delayed treatment of planktonic and biofilm cells with novel gel showed better efficacy as compared with conventional gel in S. aureus-infected burn wound. Histopathological analysis also showed better skin healing efficacy of novel gel than conventional gel. Our results show that moxifloxacin can be efficiently used topically in the management of burn wound infections along with other antibacterial agents. Since biofilm-mediated infections are on the rise especially in chronic bacterial disease, therefore, a preparation containing antibiofilm agent-like Boswellia as one of the excipients would be more meaningful.

Polycaprolactone-based neurotherapeutic delivery of rasagiline targeting behavioral and biochemical deficits in Parkinson's disease.

Rasagiline mesylate is an irreversible MAO-B inhibitor which requires daily oral administration for treatment of Parkinson's disease due to its short half-life. Patients with Parkinson's disease also develop dysphagia, i.e., difficulty in swallowing. Encapsulating rasagiline in polycaprolactone microspheres can alleviate the problem of daily oral administration by prolonging drug release from polymeric microspheres for 1 month by single subcutaneous administration. Polycaprolactone shows absence of any acidic environment generation during its degradation in body which is its advantage over poly (lactic-co-glycolic) acid. Exploiting pH-based solubility of rasagiline mesylate pH changes during microencapsulation process was performed to fabricate rasagiline mesylate-loaded polycaprolactone microspheres. Particle size analysis of microspheres showed mean particle size range of 24.18-47.87 µm. Scanning electron micrographs revealed spherical non-porous particles with small pits and depressions on the surface. In vitro release studies of formulations were performed to get an idea about in vivo behavior of prepared formulations. Stereotaxic rotenone model was used to study in vivo efficacy of formulation in rats. Selected formulation significantly (p < 0.05) improved various behavioral (locomotor activity, grip strength, etc.) and biochemical (lipid peroxidation, reduced glutathione, etc.) changes. Polymeric microspheres showed robust effect on all outcomes assessed with non-significant difference between daily administration of rasagiline mesylate solution and drug-loaded polymeric microspheres administered once in a month. With prepared controlled release injectable once a month, administration is required making it an interesting and convenient approach in treatment of Parkinson's disease with dysphagia. Patient compliant system can be achieved by exploiting this approach for future use.

Use of thermal and non thermal techniques for assessing compatibility between mirtazapine and solid lipids.

The present investigation was aimed at the evaluation of possible interactions between mirtazapine and selected solid lipids that are commonly used to develop solid lipid nanoparticles (SLNs) and nanostructured lipidic carriers (NLCs). The solids lipids explored were palmitic acid, stearic acid, glycerylmonostearate, cutina CPPH, sterotex NF, gelucire 50/13, hydrogenated castor oil and compritol 888 ATO. The techniques used were Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Hot Stage Microscopy (HSM) and Isothermal Stress Testing (IST) studies. In some cases, the DSC results indicated the possibility of drug-solid lipid interactions which was further ruled out by performing HSM studies. Moreover, IST studies were also used to further confirm the compatibility between the drug and selected solid lipids. And the findings from these studies indicated compatibility between mirtazapine and solid lipids that can further be used to develop SLNs or NLCs.

Antidepressants as antipruritic agents: A review.

Pruritus is a concomitant symptom of various underlying disorders viz. dermatological, systemic and psychiatric disorders that provoke the person to scratch the skin. Many natural as well as, antipruritic therapies are usually practiced in the treatment of pruritus including general preventive measures, topical therapies such as cooling agents, antihistamines, anesthetics, capsaicin, corticosteroids, immunomodulators and; systemic therapies including administration of antihistamines, opioid antagonists/agonists, antiepileptic drugs/neuroleptics (e.g., gabapentin and pregabalin), antidepressants (e.g., doxepin, amitriptyline, paroxetine, fluvoxamine, sertraline, escitalopram and mirtazapine) (Patel and Yosipovitch, 2010; Reich et al., 2011; Martín and Padilla, 2015; Eskeland et al., 2016). Topical therapies are the mainstay of treatment of delicate and localized pruritus while other systemic drug therapies are used to treat stern and generalized pruritus. The reported antipruritic activity of some antidepressant drugs has intrigued this review to focus on the types of pruritus, pruritus mechanism, the antipruritic mechanism of antidepressants and to comprehend the role of antidepressants in the management of pruritus.

Assessment of improved buccal permeation and bioavailability of felodipine microemulsion-based cross-linked polycarbophil gel.

The oral bioavailability of felodipine (FEL) is very low, i.e., about 15%. This could be due to low water solubility and hepatic first-pass effect. The objective of the present study was to develop FEL microemulsion-based gel, to bypass the first pass effect, for buccal delivery. The optimized FEL microemulsion (OPT-MEF) was used to prepare buccoadhesive gels, with varying concentrations of hydroxypropyl methylcellulose (HPMC) E4M and polycarbophil (PCP), and evaluated. The cross-linking of the PCP gelling agent was done by adjusting the pH with a neutralizing agent, triethanolamine (TEA). The formulations, namely drug suspension, OPT-MEF, microemulsion-based buccal gel containing 1% w/v (MEF-E4M1), 2% w/v (MEF-E4M2), and 3% w/v (MEF-E4M3) of HPMC K4M and 1% w/v (MEF-PCP1), 2% w/v (MEF-PCP2), and 3% w/v (MEF-PCP3) of PCP were prepared and optimized on the basis of ex vivo permeation study, mucoadhesion force, and viscosity. The optimized buccal gel (MEF-PCP1) showed significantly higher (p < 0.01) permeation flux (J = 0.44 ± 0.16 mg/cm2/h), when compared with the drug suspension (J = 0.17 ± 0.14 mg/cm2/h). The permeation enhancement ratio of MEF-PCP1 was found to be 2.59 times higher than that of the aqueous suspension of the drug. The texture profile analysis of MEF-PCP1 was performed which showed spreadability (3.2 mJ), extrudability (151.8 mJ), hardness (13.8 g), and adhesiveness (41.0 g), and results indicated good spreadability and adhesiveness. The rheological study revealed the pseudoplastic flow behavior of MEF-PCP1 buccal gel. The Cmax value 9.21 ± 2.88 µg/ml of MEF-PCP1 gel was found to be significantly higher (P < 0.01) compared to the same dose administered by oral route (Cmax value 3.51 ± 1.74 µg/ml). The relative bioavailability (Fr) of the optimized MEF-PCP1 buccal gel was about 397.39% higher than that of oral route. In conclusion, consistent and effective buccal gel containing optimized FEL-loaded microemulsion, with improved buccal permeation and pharmacokinetic parameters was developed successfully to improve the bioavailability of FEL.

Augmented bioavailability of felodipine through an α-linolenic acid-based microemulsion.

The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal permeability than a BCS class I drug, and hepatic first-pass metabolism of the drug. Many drugs are unpopular due to solubility issues. The goal of this study was to develop and optimize a felodipine-containing microemulsion to improve the intestinal permeability and bioavailability of the drug. The felodipine microemulsions were developed with the selected components, i.e., α-linolenic acid as the oil phase, Tween 80 as a surfactant, and isopropyl alcohol as co-surfactant using Box-Behnken design and characterized for in vitro release and particle size. The optimized felodipine-loaded microemulsion was investigated for physicochemical interaction, surface morphology, intestinal permeability, rheology, cytotoxicity, cellular uptake, pharmacodynamic (electrocardiogram and heart rate variability), and pharmacokinetic studies to explore its suitability as a promising oral drug delivery system for the treatment of hypertension. The optimized felodipine-loaded microemulsion showed significantly higher (P < 0.05) apparent permeability coefficients (Papp) at 7.918 × 10-5 cm/s after 1 h, when compared with conventional formulations that are marketed tablet, drug oily solution, and drug emulsion, which showed a maximum Papp of 3.013, 4.428, and 5.335 × 10-5 cm/s, respectively. The optimized felodipine-loaded microemulsion showed biocompatibility and no cytotoxicity. Cellular uptake studies confirmed payload delivery to a cellular site on the J774.A1 cell line. The rheology study of the optimized felodipine-loaded microemulsion revealed Newtonian-type flow behavior and discontinuous microemulsion formation. In pharmacodynamic studies, significant differences in parameters were observed between the optimized felodipine-loaded microemulsion and marketed formulation. The optimized felodipine-loaded microemulsion showed significantly higher (p < 0.01) C max (7.12 ± 1.04 µg/ml) than marketed tablets (2.44 ± 1.03 µg/ml). It was found that AUClast obtained from the optimized felodipine-loaded microemulsion (84.53 ± 10.73 µg h/ml) was significantly higher (p < 0.01) than the marketed tablet (27.41 ± 5.54 µg h/ml). The relative bioavailability (Fr) of the optimized felodipine-loaded microemulsion was about 308.3% higher than that of the marketed formulation. The results demonstrate that the prepared microemulsion is an advanced and efficient oral delivery system of felodipine for the management of hypertension.

Universal Hearing Screening in Newborns Using Otoacoustic Emissions and Brainstem Evoked Response in Eastern Uttar Pradesh.

The objectives were to determine the incidence of hearing impairment in a standardized population of neonates and to determine the significance of association of epidemiological and risk factors with neonatal hearing loss. A cohort of 600 newborns was selected for study and divided into two groups-525 in 'No Risk' group and remaining 75 in 'At Risk' group. The study protocol was carried out in three steps: (a) Screening of Hearing Loss with TOAE, done from 36 h after birth to 28 days of life, (b) Re-screening of hearing loss in newborns (of 4-12 weeks of age), who were tested positive for hearing loss in the first screening, done with DPOAE, (c) Confirmation of hearing loss with BERA, in those who were tested positive in both the first and second screening. In the study the incidence of hearing impairment in 600 infants screened was 6.67 per 1000 screened; 3.81 per 1000 screened in the Not at Risk group and 26.67 per 1000 screened in At Risk group. In At Risk group, admitted to the NICU, severe birth asphyxia and hyperbilirubinemia were found to be major risk factors. Loss to follow up was more in Not at Risk group and False Positive cases with TEOAE were more than DPOAE. BERA was found to be must for confirmation of hearing loss. Neonatal Hearing Screening of only At Risk population is likely to miss some hearing loss. Universal Hearing Screening should be the preferred strategy. Good follow up in the 'At Risk' group suggests that initial interventions in NICU had sensitized the parents for the possibility of hearing loss. This study recommends the introduction of two stage neonatal screening-rescreening protocol, using OAE and BERA, in the country in phased manner.

Lipid Nanocarrier: an Efficient Approach Towards Ocular Delivery of Hydrophilic Drug (Valacyclovir).

This research focuses on the fabrication and evaluation of solid lipid nanoparticles (SLNs) for improved ocular delivery of valacyclovir (VAC). Stearic acid and tristearin were selected as the lipid carrier while Poloxamer 188 and sodium taurocholate were used as surfactant and co-surfactant, respectively. The physiochemical properties of the optimized batch (SLN-6) fulfil the prerequisites needed for an ideal ocular formulation like submicron size (202.5 ± 2.56 nm), narrow PDI (0.252 ± 0.06), high zeta potential (-34.4 ± 3.04 mV) and good entrapment efficiency (58.82 ± 2.45%). The in vitro release study of SLN-6 exhibited a sustained release profile (>60% in 12 h). The ex vivo studies performed on excised cornea exhibited enhanced drug permeation of SLNs (22.17 ± 1.41 µg/cm2 h) in comparison to the drug solution (3.78 ± 1.34 µg/cm2 h). Apart, the corneal hydration studies, histopathology and Hen's Egg Test Chorio Allantoic Membrane (HETCAM) assay, confirmed the non-irritancy of SLNs. The in vivo study confirmed improved ocular bioavailability of VAC from SLN-6 (AUC0-12: 856.47 ± 7.86 µg h/mL) in contrast to the drug solution (AUC0-12: 470.75 ± 8.91 µg h/mL). Hence, the overall studies suggested the potential of SLNs in efficient ocular delivery of a hydrophilic molecule like VAC.

Polymer based microspheres of aceclofenac as sustained release parenterals for prolonged anti-inflammatory effect.

Poly(lactic-co-glycolic acid) (PLGA) (75:25) and polycaprolactone (PCL) microspheres were fabricated for prolonged release of aceclofenac by parenteral administration. Microspheres encapsulating aceclofenac were designed to release the drug at controlled rate for around one month. Biodegradable microspheres were prepared by solvent emulsification evaporation method in different polymer:drug ratios (1:1, 2:1 and 3:1). After drug loading, PLGA and PCL microspheres showed a controlled size distribution with an average size of 11.75µm and 3.81µm respectively and entrapment efficiency in the range of 90±0.72% to 91.06±4.01% with PLGA and 83.01±2.13% to 90.4±2.11% with PCL. Scanning electron microscopy has confirmed good spherical structures of microspheres. The percent yield of biodegradable polymeric microspheres ranged between 30.95±10.14% to 92.84±3.15% and 47.33±4.72% to 80±3.60% for PLGA and PCL microspheres respectively. PLGA microspheres followed Higuchi release pattern while Korsmeyer-Peppas explained the release pattern of PCL microspheres. Stability studies of microspheres were also carried out by storing the preparations at 2-8°C for 30, 60 and 90days and evaluating them for entrapment efficiency, residual drug content and polymer drug compatability. In-vivo studies showed significant anti-inflammatory activity of microspheres upto 48hours using the carrageenan induced rat paw oedema model.