OCULAR DELIVERY OF NATAMYCIN SOLID LIPID NANOPARTICLE LOADED MUCOADHESIVE GEL: FORMULATION, CHARACTERIZATION AND IN VIVO STUDY

Objective: This study aimed to develop a novel topical ocular system of natamycin (NAT) by formulating and evaluating of NAT-solid lipid nanoparticle (SLN) loaded on mucoadhesive gels to improve its therapeutic activity and reduce the frequency of dosage to assist patient compliance. Methods: SLNs were prepared using lipids and Tween 80 or Pluronic F127 as stabilizers via modified high shear homogenization and ultrasound techniques. The prepared SLNs were characterized for particle size (PS), zeta potential (ZP), polydispersity index (PI), and entrapment efficiency percentage (EE %). The morphological examination for chosen SLNs was done using a transmission electron microscope (TEM). Carbapol 940 and Hydroxypropyl methylcellulose (HPMC) was incorporated with selected NAT-SLNs to form mucoadhesive gels. The prepared NAT-SLN gels were evaluated for drug content, mucoadhesion force, release study, and in vitro microbiological activity. In vivo study for the chosen formulae was done to evaluate its efficacy against keratitis in rabbits. Results: NAT-SLNs exhibited high EE % up to 99.167% and PS ranging from 128.35 to 1719.5 nm, with negatively charged ZP that confirmed the stability of SLNs. The NAT-SLN gels provided the high mucoadhesive force with a controlled release manner compared with the marketed-product MP. The in vivo experimental studies and histopathological examination showed the superiority of G2 (NAT-SLN (5% Pluronic F127 and 1:1 mixed lipid) 4% HPMC) over MP against Candida keratitis. Conclusion: According to the obtained results, G2 provided an effective pharmaceutical system against fungal keratitis in a controlled release manner compared with MP for reducing dosage frequency

A New Combination Formula for Treatment of Fungal Keratitis: An Experimental Study

Objective. To formulate and evaluate slow release ketoconazole and ketorolac to treat fungal keratitis and associated inflammation. Methods. Experimental study with the following outcome measures. Pharmaceutical Evaluation. Mucoadhesive gels containing ketoconazole and ketorolac were used. Microbiological in vitro evaluation was performed using cup method. In vivo evaluation was performed on 24 rabbits divided into 2 groups, 12 rabbits each, group A (fast release formula; 6 times daily) and group B (slow release formula; 3 times daily). Each group was divided into two subgroups (6 rabbits each). Both eyes of rabbits were inoculated with Candida albicans. The left eye of all rabbits received the combination formulae. The right eye for one subgroup received ketoconazole as control 1 while the other subgroup received placebo as control 2. Clinical follow-up was done and, finally, the corneas were used for microbiological and pathological evaluation. Results. Gels containing high polymer concentration showed both high viscosity and mucoadhesion properties with slower drug release. The infected eyes treated with slow release formula containing both drugs showed better curing of the cornea and pathologically less inflammation than eyes treated with fast release formula. Conclusion. Slow release formula containing ketoconazole and ketorolac showed higher activity than fast release formula against fungal keratitis and associated inflammation

NIOSOMES VERSUS PRONIOSOMES AS PROMISING DRUG DELIVERY SYSTEMS IN TREATMENT OF DIABETES MELLITUS

Diabetes Mellitus (DM) has emerged as an epidemic that has affected millions of people globally in the last few decades. Conventional antidiabetic dosage forms have a lot of problems that necessitate searching for novel drug delivery systems to overcome these drawbacks. Niosomes and proniosomes have been used to carry a wide variety of antidiabetic drugs achieving controlled and sustained release, which improves patient compliance. This review article describes the fundamental aspects of niosomes and proniosomes, including their structural components, methods of preparation, advantages and drawbacks, characterization, factors affecting niosomes formation along with their application in the treatment of diabetes. It also highlights the participation of other drug delivery systems in the treatment of diabetes done, mainly in the last decade

BINGE EATING DISORDERS; UPDATED AND EMERGING APPROACHES

Objective: Binge eating disorders (BED) recently become a global health care issue for clinicians with detrimental effects on all organ systems. A multidisciplinary strategy including pharmacotherapy is required for its management. Methods: This review is intended to comparatively evaluate the relative efficacy of different pharmacological agents in BED treatment with new therapeutic approaches, focusing on the clinical evidence and on Phase III randomized controlled trials. Results: Data suggest that certain treatments have advantages over placebos to reduce binge eating features; however, the small duration of such research with the lack of adequately sized trials was the major limitation in interpreting these findings. Furthermore, these medications are mostly not greatly efficient for BED associated with obesity except for topiramate, which markedly improves the features of binge episodes with weight loss. Till now, lisdexamfetamine is still the only drug with regulatory permission for BED therapy; however, its weight loss efficacy has not been established. Conclusion: Drugs alone or in combination approaches may be useful pharmacotherapies to yield promising outcomes acutely and over longer-term follow-up in the treatment of BED

Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies

Being one of the highly effective drugs in treatment of Alzheimer’s disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478 ± 4.94 nm) with a nearly neutral zeta potential (ZP, −8 ± 0.2 mV) and an entrapment efficiency percentage of 48 ± 6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels

NANO-DELIVERY SYSTEMS FOR ENHANCING ORAL BIOAVAILABILITY OF DRUGS

The two main issues impacting oral delivery are drug solubility and permeability. The FDA adopted the Biopharmaceutics Classification System (BCS) in 2000. The BCS categorizes drugs into four classes based on their solubility and permeability. For permeability improvement and bioavailability, many experimental systems are utilized. Numerous nanocarrier technologies have recently been utilized to increase drug permeability by employing nanocarrier systems such as lipid vesicles, polymeric and lipid nanoparticles, polymeric micelles, and submicron lipid emulsions. This review proposes innovative nano-delivery systems for permeability augmentation. It focuses on some illustrations of drugs with various nanosystems, how these systems were developed, and how they successfully boost intestinal drug permeability and bioavailability

PREPARATION AND EVALUATION OF ONCE DAILY FLOATING GMO-ALGINATE MICROSPHERES CONTAINING FAMOTIDINE

Objective: In this work, a gastro-retentive floating microsphere delivery system composed of Drug/ Glyceryl mono-oleate (GMO) embedded in a Ca-alginate gas-generated matrix was designed to improve the bioavailability of a slightly-soluble model drug Famotidine. Methods: The water/Oil emulsion method was used to prepare Famotidine floatable microspheres, and formulation variables such as Alginate: GMO ratio, gas-generated bicarbonates concentration, and loading drug concentration were investigated. Conventional techniques including DSC, XRD & FTIR were performed to confirm Famotidine compatibility with GMO and Alginate polymers. Real-Time X-ray Radiography was used for in-vivo imaging of Famotidine floatable microspheres using rabbits as an animal model. HPLC spectroscopic technique was used to determine Famotidine plasma concentration after oral administration of Alginate-GMO loaded microspheres. Results:  Floating Famotidine Alginate-GMO microspheres (0.75:1:0.25) w/w/w showed a remarkable entrapment efficiency (>98%), good buoyancy (>84) and prolonged in-vitro drug release properties (>24hours). DSC, XRD, & FTIR techniques showed no evidence of interaction between Famotidine and Alginate or GMO. In-vivo Imaging of Famotidine floatable microspheres showed that capsules containing Famotidine-Alginate microspheres were not detected after 3hrs of administration, while capsules containing Famotidine-GMO-Alginate microspheres can be detected for more than 12hrs, indicating superior gastric retention properties. The pharmacokinetic parameters were calculated for Famotidine: GMO-Alginate, and Famotidine: alginate, and compared with the plain drug over 24 h period. Famotidine: GMO-Alginate microspheres exhibited controlled and prolonged absorption Tmax of 6.0 vs. 3.0 and 2.0 hrs; Cmax of 124.9±0.9 vs. 323.7±0.4and 458.6±0.5 ng/ml; AUC0-24 of 2153.025±6.7 vs. 1650.4±1.9 and 1110.725±2.1 ng/ml for Famotidine: alginate and plain drug, respectively, reflecting the increase in the bioavailability of the drug in the floating formulations compared to the free drug. Conclusion: Prolonged gastric retention time and sustained release properties of floating GMO-alginate microsphere suggest that it could provide a valuable sustained release dosage form of slightly-soluble drugs

OPTIMIZING LEVETIRACETAM SURFACTANT-BASED NANOVESICLES (LEV-NVS) GEL FOR TREATING EPILEPSY USING EXPERIMENTAL DESIGN

Objective: To develop and estimate the intranasal delivery of Levetiracetam surfactant-based nanovesicles (Lev-Nvs) as a brain-targeted antiepileptic delivery system prepared via solvent evaporation technique. Methods: Optimized formulation F (OPT) chosen by the Design-Expert® program gave the highest entrapment efficiency (EE%) was  incorporated into the gel. An experimental design was adopted utilizing various (span 65) surfactants and different cholesterol ratios.The (Lev-Nvs) nanovesicles were formulated by solvent evaporation technique and evaluated for in-vitro characterization parameters such as zeta sizer,Transmission Electron Microscopy (TEM), zeta potential .The nasal gel was evaluated for drug-excipient interactions utilizing Fourier Transform Infrared Spectroscopy (FTIR) and subjected to in-vitro and in-vivo release studies, Results: The results indicated that the entrapment efficiency (EE%) of Levetiracetam surfactant-based nano-vesicles (Lev-Nvs) could be modulated by the alterations in surfactant and cholesterol concentrations. Optimized formulation F (OPT) showed an entrapment efficiency of (87.9 ± 1.06 %), (206.7 ± 20.43 nm) particle size, (-34.1) zeta potential and (0.979) PDI. The nanovesicle nasal gels of the F(OPT) were prepared using Carbopol 940 at different concentrations. G 0.375 formulation showed the best in vitro drug release (87.36%) after 12 hrs. Finally, the comparative in vivo pharmaco-kinetics release studies on rats revealed considerable, sustained release of the nanovesicle nasal gel and higher relative bioavailability than an equivalent dose of oral solution (293.85%). Conclusion: Our study proves the improved efficacy of Levetiracetam as a surfactant-based nanovesicle intranasal gel in the brain targeting antiepileptic medication

Sertaconazole-Nitrate-Loaded Leciplex for Treating Keratomycosis: Optimization Using D-Optimal Design and In Vitro, Ex Vivo, and In Vivo Studies

This study aims to develop efficient topical therapy for keratomycosis using sertaconazolenitrate (STZN)-loaded leciplex (LP). The D-optimal design was used to optimize STZN-loaded LP by utilizing soy phosphatidylcholine (SPC) molar ratio (X1), cationic surfactant molar ratio (X2), and cationic surfactant type (X3) as the independent variables, whereas their impact was studied for entrapment efficiency percent (EE; Y1), particle size (PS; Y2), polydispersity index (PDI; Y3), zeta potential (ZP; Y4), and permeability coefficient (Kp; Y5). The optimized formula was evaluated regarding morphology, ex vivo permeation, mucoadhesion, stability, and in vivo studies. The optimized formula was spherical and showed EE of 84.87 ± 1.71%, PS of 39.70 ± 1.35 nm, PDI of 0.242 ± 0.006, ZP of +54.60 ± 0.24 mV, and Kp of 0.0577 ± 0.0001 cm/h. The ex vivo permeation study revealed that the optimized formula enhanced the Kp and corneal deposition by 2.78 and 12.49 folds, respectively, compared to the aqueous drug dispersion. Furthermore, the optimized formula was stable and revealed promising mucoadhesion properties. Finally, the in vivo studies showed that the optimized formula was superior to the drug dispersion in treating rats with induced keratomycosis. These results confirmed the capabilities of LP as a promising nanocarrier for treating ocular diseases topically

THE EFFECT OF CO-PROCESSED EXCIPIENTS DURING FORMULATION AND EVALUATION OF PEDIARIC LEVETIRACETAM ORODISPERSIBLE TABLETS IN RATS

Objective: The main aim of this research was to make cost-effective taste-masking oral pediatric orodispersible tablets (ODTs) of Levetiracetam as an antiepileptic drug (AED) using various co-processed excipients by direct compression method. Methods: Eight kinds of ready-made co-processed excipients in addition to sucralose and menthol as a sweetener were utilized. The weight variation, drug content, friability, in-vitro disintegration, dissolution time, hardness, thickness, and pharmacokinetics of the produced ODTs were determined. Results: The optimized formula (F5) containing Pharmaburst® 500 showed the shortest disintegration time (11.66 sec) and more than 98% of Levetiracetam within 10 min(Q10). The Pharmacokinetic study of this optimum formula (F5) in rats using HPLC-UV detector showed 26.904 ± 2.027ng/ml as the Cmax and 101.935 ± 0.894 hr.ng/mL as AUC compared to commercial Tiratam® solution 10.421 ± 0.295ng/ml and 23.135 ± 0.43 hr.ng/mL respectively. Conclusion: Levetiracetam orally orodispersible tablets were successfully prepared with acceptable hardness, satisfactory taste, and rapid disintegration in the oral cavity avoiding first-pass metabolism to yield the desired rapid effect in facing epilepsy for patients who experience dysphagia like pediatric and geriatric. In addition to the unconsciousness of the epileptic patient followed the seizure attack