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Transdermal drug delivery has been widely adopted as a plausible alternative to the oral route of administration, especially for drugs with poor systemic bioavailability. The objective of this study was to design and validate a nanoemulsion (NE) system for transdermal administration of the oral hypoglycemic drug glimepiride (GM). The NEs were prepared using peppermint/bergamot oils as the oil phase and tween 80/transcutol P as the surfactant/co-surfactant mixture (Smix). The formulations were characterized using various parameters such as globule size, zeta potential, surface morphology, in vitro drug release, drug-excipient compatibility studies, and thermodynamic stability. The optimized NE formulation was then incorporated into different gel bases and examined for gel strength, pH, viscosity, and spreadability. The selected drug-loaded nanoemulgel formulation was then screened for ex vivo permeation, skin irritation, and in vivo pharmacokinetics. Characterization studies revealed the spherical shape of NE droplets with an average size of ~80 nm and a zeta potential of −11.8 mV, which indicated good electrokinetic stability of NE. In vitro release studies revealed enhanced drug release from the NE formulation compared to the plain drug. GM-loaded nanoemulgel showed a 7-fold increment in drug transdermal flux compared to plain drug gel. In addition, the GM-loaded nanoemulgel formulation did not elicit any signs of inflammation and/or irritation on the applied skin, suggesting its safety. Most importantly, the in vivo pharmacokinetic study emphasized the potential of nanoemulgel formulation to potentiate the systemic bioavailability of GM, as manifested by a 10-fold rise in the relative bioavailability compared to control gel. Collectively, transdermal NE-based GM gel might represent a promising alternative to oral therapy in the management of diabetes.

Aim: The aim of this study was to design fast dissolving tablets (FDT) of the anti -psychiatric drug, Haloperidol in liquisolid forms as a way to enhance its dissolution profile and anti-psychiatric effect. Methodology: Solubility studies of Haloperidol in various solvents and surfactants were conducted. The solvent with high solubilizing ability was tween 20 (80%), selected and absorbed into the carrier and then coating material added with other solid powder excipients, finally all powder compressed into tablets. The resulting liquisolid tablets were evaluated according to British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies through forced swimming test (FST). Results: Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with haloperidol. The selected liquisolid tablet (LS4) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. Attempts of in vivo dissolution results and thermodynamic stability studies showed acceptable results for the F4 formulation containing 80% Tween 20,Avicel and aerosel (0.22:81.6:10.2%), respectively. The in vivo study of (LS4) formulation revealed the highest immobility time to rats compared to control rats and others treated with purchased halonace®. Conclusion: Fast dissolving liquisolid tablets expressed rapid onset of action with enhanced anti-psychiatric effect of haloperidol.

Background: Asthma is the most common chronic inflammatory disease of the pulmonary system. The prevalence of asthma is growing enormously worldwide posing a significant health and economic burden. Asthma treatment guidelines recommend a combination of inhaled corticosteroid (ICS) and long-acting beta 2 agonist (LABA). However, there is little guidance for clinicians on selecting a specific ICS/LABA combination. Aim: To compare the effectiveness of three fixed dose ICS/LABA combination therapies i.e., fluticasone/salmeterol, fluticasone/formoterol and budesonide/formoterol for the management of moderate to severe asthma. Design: This was a prospective interventional, three-armed, parallel group, open label, and randomized clinical trial Methods: Adult asthmatic patients of both genders (n=135) were randomly allocated to the three ICS/LABA treatment groups: fluticasone/salmeterol-treated group (n=45) , fluticasone/formoterol-treated group (n=45) and budesonide/formoterol-treated group (n=45). All groups were treated for three months. The main outcome parameters included lung function (FEV1, FEV1%, FEV1/FVC), inflammatory state (hs-CRP, ECP) and asthma control (ACT). Results: After 3 months of treatment, fluticasone/formoterol significantly increased FEV1 compared to fluticasone/salmeterol (p

One of the widely efficient and noteworthy nanocarriers that could draw a great attention toward pharmaceutical fields is nanoemulsions (NEs). NEs are thermodynamically stable colloidal dispersions composed of two immiscible liquids, oil and water that mixed together using emulsifying agent (surfactant and co-surfactant). It regarded as pharmaceutical dosage form having droplet size within a nanometer range, hence it has extensively considered as carrier for delivering active agents. Such carrier is fabricated in order to overcome some obstacles associated with conventional drug delivery systems especially low bioavailability. The objective of this review is to present an overview about NE and its latest applications in diverse areas such as drug delivery, cosmeceutical and nutraceutical. Clarifications about different mechanisms of NEs development that are frequently used were provided. Correspondingly, popular characterization techniques for NEs such as determination of particle size, polydispersity index (PDI), zeta potential and viscosity were reviewed. Eventually, summary of physical and chemical instability in addition to the regulatory aspects of NE were provided.

Self-nanoemulsifying drug delivery systems (SNEDDS) in both liquid and solid forms were suggested to improve water solubility of Doxazosin mesylate (DOX) a poorly water- soluble antihypertensive drug. Oleic acid: Smix (1:9 w/w) and Tween 80: co-surfactant mixture (Ethanol and PEG 400) (1:1, 2:1, 3:1 and 4:1) were chosen to prepare a liquid and solid forms of SNEDDS according to their solubility. TEM images revealed change in the crystalline nature of DOX into uniform particles with smooth surface. Characterization studies revealed droplet size ranges from 79.80±14.39 to 273.10±4.17 nm, zeta potential ranges from -5.57±0.10 to -21.13±0.46 mV and dissolution enhancement of more than two folds with more favorable properties for the solid forms. FTIR demonstrated significant physical changes in DOX crystalline structure. In conclusion, the solid SNEDDS containing oleic acid: Smix (1:9 w/w) and Tween 80: co-surfactant mixture (3:1 w/w) and adsorbent mixture of Avicel 101 and Aerosil 200 (40:1 w/w) might be a promising formula for better management of hypertension with expected shelf stability.

The application of nanotechnology to drug delivery systems for cancer therapy has progressively received great attention. The most heavily investigated approach is the development of nanoparticles (NPs) utilizing biodegradable and biocompatible polymers such as poly (lactic-co-glycolic acid) (PLGA). These NPs could be further improved by surface modification utilizing a hydrophilic biodegradable polymer such as polyethylene glycol (PEG) to achieve passive targeting. Modified NPs can deliver drugs such as brucine (BRU), which has shown its potential in cancer therapy. The objective of the current investigation was to develop and evaluate the passive targeting of long-circulating PLGA NPs loaded with BRU. NPs were characterized in terms of drug-excipient compatibility studies, including FTIR and DSC; physicochemical evaluations including particle size, zeta potential, morphological evaluation, entrapment efficiency and percentage yield; total serum protein adsorbed onto NP surfaces; and in vitro release of the loaded drug. Factorial design was employed to attain optimal PLGA-loaded NPs. Finally, the in vivo anti-tumor activity of BRU-loaded PLGA NPs was evaluated in tumor-bearing mice. The NPs obtained had smooth surfaces with particle sizes ranged from 94 ± 3.05 to 253 ± 8.7 nm with slightly positive surface charge ranged from 1.09 ± 0.15 to 3.71 ± 0.44 mV. Entrapment of BRU ranged between 37.5 ± 1.8% and 77 ± 1.3% with yields not less than 70.8%. Total protein adsorbed was less than 25.5 µg total protein/1 mg NP. In vitro drug release was less than 99.1% at 168 h. Finally, significant reductions in tumor growth rate and mortality rate were observed for PEG PLGA NP formulations compared to both BRU solution and naked NPs.

The aim of the study was to design a self-emulsifying drug delivery system (SEDDS) of the anti-hypertensive Carvedilol in liquid and liquisolid forms as a way to enhance its dissolution profile and anti-hypertensive effect.Solubility studies of Carvedilol in various oils, surfactants and co-surfactants were conducted, followed by the construction of pseudo-ternary phase diagrams and other in vitro assessments. The selected SEDDS formulation (S1) was adsorbed onto solid powder excipients and compressed into tablets. The resulting liquisolid tablets were evaluated under British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies in hypertensive rats.Attempts of self-emulsification, droplet size, and thermodynamic stability studies showed acceptable results for the S1 formulation containing Capryol 90, Tween 20, and Transcutol HP (10:53.3:26.2%), respectively. Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with Carvedilol. The selected liquisolid tablet (LS7) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. A significantly (p .05) fast dissolution rate was observed for both SEDDS and liquisolid formulations when compared to pure drug and marketed CarvepressSelf-emulsifying liquisolid tablets expressed rapid onset of action with enhanced anti-hypertensive effect of Carvedilol.

Doxazosin Mesylate (DOX) is an antihypertensive drug which possesses poor water solubility and hence low bioavailability. The study objective is to prepare DOX fast disintegrating tablets as a new dosage form for geriatric patients. First, 23 full factorial design using Polyvinyl pyrrolidone k 30, Poloxamer-407 and Sodium Lauryl Sulphate at low and high ratios were used for preparation of DOX nanosuspension as a trial to improve its dissolution properties. Nanosuspension formulations were characterized using Transmission electron microscopy, Differential scanning calorimetry and Fourier transform infrared spectroscopy. Then, the optimized formula was incorporated in fast disintegrating tablets using different superdisintegrants. The tablets were evaluated for hardness, thickness, friability percentage, diameter, weight variation, Wetting time, disintegration time and percentage dissolution after 10 min. A significant reduction (rapidly and efficiently) in mean arterial pressure of hypertensive rats was observed for DOX nanosuspension fast disintegrating tablet using Ac-Di-Sol as a superdisintegrant with 100% dissolution after 10 min.

The present study aims to emphasize the enhanced efficacy of long acting in-situ gel forming implants (ISGFI) based on poly (lactic-co-glycolic acid) (PLGA) matrix to deliver anti-psychotic risperidone over extended time periods with reduced administration frequency. Schizophrenic patients show considerable difficulties in adherence and compliance to oral medications associated with negative outcomes including symptoms exacerbation and psychotic relapse. The studied optimized ISGFI formulation, comprised of 2.85:1 ratio of DMSO solvent:PLGA (type 75:25), was subjected to various characterization studies including morphological real-time changes, scanning electron microscopy and in-vitro drug release study. Pharmacokinetics and behavioral evaluations of anti-psychotic action of ISGFI systems were pursued on healthy and schizophrenia-induced rats respectively then compared to results of marketed microspheres. Morphological observations showed the immediate formation of whitish smooth ISGFI system owing to the rapid PLGA solidification after rapid DMSO dissipation into the external medium. Scanning electron microscopy confirmed the slow gradual biodegradation of the formed ISGFI. The optimized formulation assured its effectiveness to produce satisfactory initial burst and cumulative risperidone release and obviate costs of additional tablets needed during the commercial product use. Pharmacokinetic study manifested the effective performance of ISGFI to extend risperidone release for longer period (72 days) in comparison to the marketed formulations (48 days). Besides, optimized ISGFI were more effective in improving ketamine-induced schizophrenia-like symptoms in experimental rats, particularly in the first week of study period. Meanwhile, in-vitro, pharmacokinetic and pharmacodynamic evaluations had advocated the potential advantages of ISGFI systems for treating schizophrenia with improved adherence and compliance of patients.

Cancer represents one of the most life threatening disease worldwide. Poly ethylene glycol nanoemulsion (PEG-NE), a new drug delivery system (DDS) is widely utilized for encapsulating water insoluble drugs and delivering it into cancerous tissue following its intravenous injection. Brucine (BRU) is an effective anti-carcinogenic agent toward different cancer cell lines; however, its low solubility represents a great obstacle in its formulation. The objective of this investigation was to develop and evaluate BRU-PEG-NE. Physicochemical evaluation including, viscosity, particle size and entrapment efficiency investigations were performed. Quantitative and qualitative estimation of total serum protein adsorbed onto the surface of BRU-NE were performed. in vitro release studies of BRU-NE with and without serum incubation were assayed. Formulations were tested for their cytotoxic activity using MTT assay. Finally, in-vivo anticancer effect was evaluated in tumor-inoculated mice. Homogenous NEs were obtained with particle size less than 140 nm and viscosity less than 3.3 cP for BRU-PEG-NE. Total serum protein adsorbed was less than 17.33 ± 0.76 μg/μmol total lipid for BRU-PEG-NE. in vitro drug release was less than 65 % over 24 h for PEG-NE. As well, PEG-NEs could achieve significant inhibition for the viability of cancer cells. Finally, significant reduction in tumor growth rate and mortality rate for BRU PEG-NE formulations were obtained. The obtained results suggested that BRU PEG NE could be considered as a potential mean for cancer therapy.

We recently developed a PEG-coated liposome encapsulating the anti-folate drug pemetrexed (PMX). Such liposomal formulations have shown potent cytotoxic effects against malignant pleural mesothelioma (MPM) cells in vitro. In the present study, we investigated the pharmacokinetics, bio-distribution and in vivo anti-tumor efficacy of two liposomal PMX formulations with different drug release rates in a murine mesothelioma-xenograft model. Liposomes with different PMX release rates were prepared via manipulating liposomal membrane fluidity through incorporating either a solid-phase (HSPC) or a fluid-phase (POPC) phospholipid. Both liposomal PMX formulations showed prolonged plasma pharmacokinetics and were accumulated to a similar extent in tumors and other tissues, presumably, due to surface modification with polyethylene glycol (PEG). In a murine mesothelioma-xenograft model, interestingly, PMX encapsulated in a fast-release POPC liposome produced superior tumor growth suppression compared with either free PMX or PMX encapsulated in a slow-release HSPC liposome. Such in vivo anti-tumor efficacy was accomplished mainly by a potent induction of apoptosis within tumor tissue by the released PMX from POPC liposomes. Our results clearly emphasize the therapeutic efficacy of liposomal PMX over free PMX in conquering aggressive solid tumors such as malignant mesothelioma. A guarantee of the targeted delivery of PMX to tumor cells helps overcome some of the major shortcomings encountered with the use of free PMX.

The current study aims to develop in-situ forming implants (ISFI) of anti-psychotic risperidone to customize schizophrenia therapy. Non-adherence to treatment is the most prevalent unsuccessful clinical outcome in schizophrenic patients. Poly(lactic-co-glycolic acid) (PLGA) was utilized to prepare ISFI using various solvents having different drug solubilization capacity. 33 Box-Behnken Design (BBD) was used to study the effects of independent variables; lactide concentration (A), solvent type (B) and solvent/polymer ratio (S/P) (C) on burst release after 6h (Y1), cumulative release after 40 days (Y2) and injectability time (Y3). Statistical analysis was followed by optimization process to minimize burst release and injectability time with targeted cumulative release to 50% at 40 days. BBD results represented the critical impacts of increasing lactide and PLGA concentrations on reducing drug burst and percent release. Rapid ISFI solidification using DMSO supported the high dispersed drug encapsulation and sustained release. Triacetin demonstrated a lag time between formulation injection and solidification that negatively affected the studied responses. The optimized formulation manifested burst (8.1%), cumulative release (51.08%) and 18 s for injection by mixing PLGA (75:25) and DMSO (S/P = 2.851). Compared with injectable commercial microspheres, ISFI emphasized their potential to enhance compliance and eliminate costs issues of additional oral therapy.

Entecavir (Baraclude®) is used daily as a long-term treatment for hepatitis-B virus infections. In this study a sustained injectable biodegradable in-situ implant (ISI) and polymeric nanoparticles (NPs) of Entecavir were prepared using Poly-d,l-lactic-co-glycolic acid (PLGA) polymer and evaluated for their shape, saturation solubility, in-vitro release and in-vivo efficacy. The pharmacokinetic parameters of Entecavir formulations were studied in rats following intramuscular injection, and the data was analyzed using one-way analysis of variance (ANOVA). TEM photographs showed that the ISI had a porous surface after exposure to Sorensen phosphate buffer pH 7.4 for 24 h, and Entecavir loaded NPs had a spherical structure with a smooth surface. The entrapment efficiency of Entecavir NPs was in the range of 47.03–77.84%. The pharmacokinetic studies showed a significant reduction (p

For patient convenience, sustained release Adefovir Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres were formulated to relieve the daily use of the drug which is a problem for patients treated from chronic hepatitis-B. PLGA microspheres were prepared and characterized by entrapment efficiency, particle size distribution and scanning electron microscopy (SEM). In-vitro release and in-vivo studies were carried out. Factors such as drug: polymer ratio, polymer viscosity and polymer lactide content were found to be important variables for the preparation of PLGA Adefovir microspheres. Fourier transform infrared (FTIR) analysis and differential scanning calorimetry (DSC) were performed to determine any drug-polymer interactions. One way analysis of variance (ANOVA) was employed to analyze the pharmacokinetic parameters after intramuscular injection of the pure drug and the selected PLGA microspheres into rats. FTIR and DSC revealed a significant interaction between the drug and the polymer. Reports of SEM before and after 1 and 24 h release showed that the microspheres had nonporous smooth surface even after 24 h release. The entrapment efficiency ranged between 55.83 and 86.95% and in-vitro release studies were continued for 16, 31 and 90 days. The pharmacokinetic parameters and statistical analysis showed a significant increase in the Tmax, AUC0–t and MRT, and a significant decrease in the Cmax of the tested formulation (p

Pemetrexed (PMX) is a newly developed multi-targeted anti-folate with promising clinical activity in many solid tumors including malignant pleural mesothelioma (MPM). However, PMX does not show sufficient anti-tumor activity in vivo when used alone either due to inefficient delivery of adequate concentrations to tumor tissue or dose-limiting side effects. In order to overcome these problems and to achieve potent anti-tumor activity, PMX was encapsulated into a liposomal delivery system. In the present study, various formulations of liposomal PMX were prepared. The effect of formulation parameters on the encapsulation efficiency of PMX within liposomes was evaluated. In addition, the influence of drug release rate on the in vitro cytotoxicity was investigated. Encapsulation of PMX within liposomes was remarkably increased by the incorporation of cholesterol within liposomal membranes and by increasing the total lipid concentration. Encapsulation efficiency was found to be unaffected by the type of phospholipid used or the inclusion of a cation lipid, DC-6-14. Interestingly, encapsulation of PMX within "fluid" liposomes was found to allow efficient release of PMX from liposomes resulting in a potent in vitro cytotoxicity against MPM MSTO-211H cell line. On the other hand, entrapment of PMX within "solid" liposomes substantially hindered PMX release from liposomes, and thus PMX failed to exert any in vitro cytotoxicity. These results suggest that encapsulation of PMX within "fluid" liposomes might represent a novel strategy to enhance the therapeutic efficacy of PMX while minimizing the side effect encountered by the non selective delivery of free PMX to various body tissues.

Propolis has traditionally been used in curing infections and healing wounds and burns.The aim of this study is to formulate pluronic lecithin organogel of propolis to improve its availability and antimicrobial activity.Different organogels were prepared by using soybean lecithin, isopropyl palmitate, pluronic F127 and water. The effect of quantity of lecithin and pluronic F127 and percentage of oil phase was investigated. The organogels were evaluated for appearance, texture, pH, drug content and viscosity. In vitro release studies were carried out using cellophane membrane. Drug permeation through abdominal rat skin from organogels that showed high % drug release was compared to that from propolis suspension in distilled water. Finally, the antimicrobial activity of the selected propolis formulation against different bacterial isolates was compared with that of propolis suspension in water.Results showed that all organogel formulations except the formula containing 10% pluronic F127, showed acceptable physical properties. Drug content of organogel formulations was in the range of 97.5-100.2%. The pH of the formulations was in the range of 5.5-6.3 that suits the skin pH, indicating skin compatibility. The viscosity was in the range of 5366-8984 cp. A significant decrease in drug release from formulations was observed with increase in concentration of lecithin and pluronic F127. Decreasing oil phase percentage to 20% w/w led to a decrease in drug release from the formulation.The formula containing 3% lecithin and 20% pluronic F127 exhibited superior skin permeation and antimicrobial activity over propolis suspension in water.

6 . Buccoadhesive controlled release verapamil HCl tablets have been prepared using mucoadhesive polymers namely; sodium alginate (Na Alg), xanthan gum (XG) and gum tragacanth (GT) either alone or in combination in different ratios2:8, 8:2, 4:6 and 6:4. The prepared tablets were evaluated for their weight variation, thickness, hardness, friability and dissolution, content uniformity, swelling index, in -vitro adhesion, in-vitro drug release and in- vivo hypertension study. Tablets containing XG showed the highest swelling index and bioadhesive force. The maximum cumulative% released (100%) was observed in F7, F10 and F11 due to high percent of Na alg. The kinetics studies show that the release follows zero order kinetics except F1 that it obeyes a diffusion model. The buccoadhesive verapamil HCl tablet had suggested being promising for the transmucosal delivery of verapamil HCl and allowing a controlled drug delivery for6 hrs.

SUMMARY This study was conducted to investigate the effect of zinc sulfate and zinc methionine supplementation on the digestion coefficients, nutritive value, ruminal and some blood parameters, milk yield and milk composition of Friesian dairy cows. Animals were fed according to the NRC feed allowances for dairy cattle (1989). Fifteen Friesian dairy cows were divided into three groups (five animal each). Animal were fed on the following rations: Control group fed concentrate feed mixture (CFM), berseem (Trifolium alexandrinum) hay and rice straw without zinc supplementation. The 1 st tested group was fed control ration + 40mg zinc sulfate /kg dry matter intake (DMI) and the 2 nd tested group was fed control ration +40mg zinc methionine /kg DMI. All groups were fed for a period from the expected calving date to 182 days of their lactation season. Results indicated that the addition of zinc improved the nutrient digestibilities and feeding values as TDN and DCP. Also, zinc supplements tended to reduce ammonia-N and somatic cell counts but increased TVFA's, improved feed efficiency and milk yield. Moreover, zinc supplementation improved serum total protein and globulin, but reduced the concentration of both albumin and urea in blood serum.

In this research, rifampicin suppositories were prepared due to the easy use of suppository administration in the elderly and the fact that plasma concentrations are higher than tablets. The suppositories were formulated with 100 mg of rifampicin using different bases, namely Witepsol H15, Witepsol S58, Witepsol E76, Polyethylene glycol PEG (two different formulations) and modified glycerogelatin (MGG) using the melting method. To optimize the drug release rate, different enhancers such as sodium lauryl sulfate (SLS) as an ionic surfactant, as well as Brij 92 as non-ionic surfactants, and Cetrimide as a cationic surfactant in different concentrations were chosen. The highest release of rifampicin was observed with formulations containing 0.4% SLS in Witepsol S58, 1.2% Cetrimide in Witepsol S58 and 0.4% Brij 92 in PEG2. The drug plasma levels after rectal administration were compared to those obtained after oral administration of the same dose. After 4 h, C max of rifampicin was 23.91 ± 2.74 μg/mL for the oral suspension vs. 43.03 ± 1.76 and 28.90 ± 1.37 μg/mL for PEG2 with 0.4% Brij 92 and Witepsol H15 with 1.2% Brij 92 suppositories. The comparative bioavailability of rifampicin from PEG2 with 0.4% Brij 92 and Witepsol H15 with 1.2% Brij 92 suppositories were 207.42 and 148.31% respectively, in relation to that after oral administration.