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Surfactant-stabilized mucoadhesive nanogels (NGs) for vaginal delivery of fluconazole (FLZ) were studied and evaluated in this work. FLZ-NG formulations were prepared using two different types of mucoadhesive polymers, Carbopol 934 (Ca934) and Pluronic F-127 (PF127). A rheology study revealed a non-Newtonian pseudoplastic flow behavior (shear thinning) in the prepared NGs. The viscosity of Ca934 NG (0.47 Pa s) was much lower compared to the PF127 NG (6.10 Pa s). The rheology study results correlated well with the

Bacterial ghosts (BGs) are empty cell envelopes of nonliving evacuated bacterial cells. They are free from their cytoplasmic contents; however, they sustain their cellular 3D morphology and antigenic structures, counting on bioadhesive properties. Lately, they have been tested as an advanced drug delivery system (DDS) for different materials like DNA, peptides, or drugs, either single components or combinations. Different studies have revealed that, BG DDS were paid the greatest attention in recent years. The current review explores the impact of BGs on the field of drug delivery and drug targeting. BGs have a varied area of applications, including vaccine and tumor therapy. Moreover, the use of BGs, their synthesis, their uniqueness as a delivery system and application principles in cancer are discussed. Furthermore, the safety issues of BGs and stability aspects of using ghost bacteria as delivery systems are discussed. Future perspective efforts that must be followed for this important system to continue to grow are important and promising.

In this study, Pluronic F127 micellar systems have been utilized to enhance ocular delivery of ciprofloxacin (CPX) antibiotic. Critical micelle concentration of the Pluronic F127 block copolymer had been determined in isotonic phosphate buffer at pH 7.4 and in simulated lacrimal fluid (SLF) at 25 and 34 °C. Micellar systems of Pluronic F127 have been accordingly used to improve CPX solubility in isotonic phosphate buffer solution at different pH. In vitro release rate of CPX from micellar systems was investigated in SLF. Ocular delivery of selected CPX micellar formulations has been investigated and compared with that of commercially available CPX eye drops (Ciprocin®) in rabbit's eye. Pharmacokinetic parameters such as Cmax, Tmax, elimination rate constant, t1/2, MRT and AUC0 − ∞ were determined. The results of this study showed that, Pluronic F127 micellar systems have been shown to significantly improve CPX solubility in isotonic phosphate buffer solution at different pH. The viscosity of these systems was low indicating the formation of aqueous eye drops. Also, in vitro release rate of CPX was significantly higher from Pluronic F127 system prepared at pH 4.5 and 6 than that at pH 7. The investigated micellar formulations showed a significant improvement in ocular delivery of CPX compared with that of commercial CPX eye drops.

Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC0-∞, Cmax, Tmax, t1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10 h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets.

The aim of this study was to develop and evaluate ultra-fine selfnanoemulsifying drug delivery system (UF-SNEDDS) of meloxicam (MLX) to enhance its transdermal delivery. The preliminary screening was carried out to select SNEDDS components according to type IV lipid based formulations using surfactant and co-surfactant. The prepared SNEDDS formulations were subjected to different thermodynamic stability tests. The droplet size, polydispersity index (PDI), zeta potential, turbidity, transmission electron microscopy (TEM) and in vitro MLX release studies were investigated. Finally, the influence of UF-SNEDDS on the MLX transdermal delivery was assessed. These UF-SNEDDS showed droplet size range of 14.41 ± 2.50 nm to 25.58 ± 2.33 nm, PDI less than 0.3, zeta potential with negative charge and turbidity range of 1.92–3.47 NTU. TEM of reconstituted SNEDDS-F5 demonstrated dark smaller droplet with spherical shape. The in vitro MLX release from SNEDDS was found to be higher in comparison to saturated solution (control). An in vitro permeation study was achieved in rat skin, the permeated amount of MLX was increased up to 11.89-fold as compared to control. Then, the presence of surfactant and its type can influence on both the drug release and the transdermal delivery of MLX. These results indicated that UF-SNEDDS developed for transdermal delivery may be a promising delivery system for MLX, with high solubility and improved skin permeation.

The present study was undertaken to 1) formulate a pulsatile colonic delivery of simvastatin (SIM) as chronotherapy for treatment of hypercholesterolemia, and 2) enhance the dissolution profile of the prepared SIM chronotherapeutic system. Lipid based formulations were utilized to formulate SIM in capsule dosage form coated with Eudragitr hence SIMcc could be considered as successful pulsatile treatment of hypercholesterolemia. Also, dissolution profile of lipid based SIMcc was enhanced in comparison with that of SIM filled capsules.

In this study, nifedipine tablets were formulated with different types of cyclodextrins (CDs) by direct compression method. Spray dried lactose and microcrystalline cellulose (MCC) were used as tablet fillers. The prepared tablets showed good appearance with acceptable crushing strength and disintegration time. The tablets showed fast dissolution within 11 to 68 min for 80% of the drugs depending on the type of CD and tablet filler. Some of the formulated tablets presented good fast release properties similar to soft gelatin capsules (USP XXIV) and based on the calculated dissolution efficiency (DE%), tablets containing hydroxypropyl-β-CD and lactose as a filler were chosen for in vivo study by oral administration to beagle dogs when compared with the commercially available 10 mg soft gelatin capsule (Adalat®) and 10 mg film coated tablets (Corinfar ®). The formulated tablets showed significantly higher area under the curve (AUC0-∞) than the commercial soft gelatin capsule and film coated tablets as result of increased drug absorption. It was concluded that the formulated fast release tablets could replace the nifedipine soft gelatin capsules with the advantages of ease of preparation and less restricted storage and handling conditions. Key words: Nifedipine tablets, cyclodextrins, bioavailability, beagle dogs.

The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations (P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 +/- 2 degrees C) and at refrigeration temperature (4 +/- 2 degrees C) for 45 days.

Omeprazole (OME) is a proto type anti-secretary agent. This compound is very unstable, especially in acidic aqueous solutions. A stability indicating HPLC assay has been developed in order to investigate the effect of different factors on the stability of omeprazole. These factors included the pH with the tested values ranging from 6–10 and the temperature by monitoring the drug stability at 25, 37 and 40°C. The study was then extended to investigate the effect of cyclodextrins, namely beta-cyclodextrin (β-CD), dimethyl-beta-cyclodextrin (DMβ-CD), hydroxypropyl-beta-cyclodextrin (HPβ-CD) and maltosyl-beta-cyclodextrin (Mβ-CD) on the stability of omeprazole. The results showed the dependence of drug stability on the pH and temperature with the degradation being significant below pH 7 and at higher temperature. The degradation kinetics follows the first-order kinetics. The addition of different cyclodextrins accelerates the degradation of drug, and this effect was in the following manner: β-CD > DMβ-CD > Mβ-CD > HPβ-CD. The effect of different concentrations of HPβ-CD on the degradation of drug was also studied. It was noted that the degradation of drug depends on the concentration of HPβ-CD up to 1.0 mM; above this concentration the degradation was constant.

In the present work a new indomethacin (IND) self-nanoemulsifying drug delivery formulation (SNEDDF) have been prepared to enhance its dissolution which in turn could provide a better chance for IND oral absorption. IND SNEDDF have been prepared using different concentrations of castor oil as a solvent for IND, Cremophor RH 40 (Cr-40) as surfactant and Capmul MCM-C8 (Ca-8) as co-surfactant. Droplets size and turbidity of IND SNEDDFs were measured. Dissolution profile of IND SNEDDFs filled in gelatin capsules was determined by using USP apparatus 2. Ternary phase diagram was constructed to identify the self-nanoemulsifying region after evaluation of IND SNEDDFs by the visual observation. The IND SNEDDFs were thermally characterized using differential scanning calorimetry (DSC) to ensure the compatibility among its ingredients. The present study revealed that the SNEDDFs increased IND dissolution rate and has the potential to enhance its bioavailability without interaction or incompatibility between the ingredients.

Meloxicam (MLX) has poor water solubility which leads to slow absorption following oral administration; hence, immediate release tablet is unsuitable in the treatment of acute pain. The aim of this study was to prepare a novel fast ultra-fine self-nanoemulsifying drug delivery system (UF-SNEDDS) of MLX for oral administration to facilitate drug release process in the stomach as well as comparing its in vitro dissolution with commercial Mobic and Mobitil tablets. MLX solubility in oils, mixed glycerides and surfactants with different HLB values was investigated. Based on MLX solubility profiles, eight UF-SNEDDSs composed of MLX, Cremophor RH 40 as oily phase, Capmul MCM-C8 or Tween 80 as surfactant and PEG 400 as co-solvent were prepared and evaluated for their spontaneous formation of emulsion, droplet size, turbidity and in vitro dissolution. The prepared novel MLX formulations showed a significant very low droplets size (up to 25 nm), thermodynamically stable and spontaneously formed nanoemulsion. MLX UF-SNEDDS formulations showed significant high percentage of drug dissolution (up to 70%) in simulated gastric fluid, compared with Mobic and Mobitil. In conclusion, due to higher drug release from MLX UF-SNEDDS formulations they could enhance its absorption and hence its bioavailability.

Purpose : To prepare a self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate, with enhanced dissolution and better chance of oral absorption. Method : All-trans-retinol acetate SNEDDS was prepared using different concentrations of soybean oil (solvent) Cremophor EL (surfactant) and Capmul MCM-C8 (co-surfactant). Particle size and turbidity of the SNEDDS were determined after adding water to the oily solution. Dissolution profile of SNEDDS filled in hydroxyl propyl methyl cellulose (HPMC) capsules was determined by using water in USP apparatus 2. Ternary phase diagrams were constructed to identify the self-nanoemulsified region. The SNEDDS were evaluated by the visual observation, turbidity in nephrometric turbidity units (NTU), mean particle size (μm) and Fourier transformed-infrared spectroscopy (FT-IR). SNEDDS were thermally characterized using differential scanning calorimetry (DSC) to ensure the compatibility of the SNEDDS ingredient. Results : From the data obtained in this work, it was clear that surfactant to co-surfactant ratio has the main impact on the physical characteristics of the emulsion formed. The optimum surfactant to co-surfactant ratio was found to be 2:1 (37.5–50% for Cremophor EL, and 18.75–25% for Capmul MCM-C8). With this ratio, the resultant nanoemulsions obtained have a particle size range of 0.103–0.051 μm, turbidity range of 18.12–2.18 NTU and t 30 values (cumulative% all-trans-retinol acetate dissolved in 30 min) of 90.42–99.5. Also the thermograms obtained from DSC experiments showed that there is no incompatibility or interaction between the SNEDDS ingredients (soybean oil, Cremophor EL, and Capmul MCM-C8) and all-trans-retinol acetate. Conclusion : The present study revealed that the self-nanoemulsified drug delivery system of all-trans-retinol acetate increased its dissolution rate and has the potential to enhance its bioavailability without interaction or incompatibility between the ingredients.

The purpose of this investigation was to evaluate the bioavailability of three salbutamol sulfate suppository formulations. The formulations were; 2 mg salbutamol sulfate in Suppocire NA base containing 6% Eudispert gel (F1), 2mg salbutamol sulfate in Witepsol H15 base containing 3% methyl cellulose gel (F2), and 2 mg salbutamol sulfate in Witepsol W25 base containing 3% methyl cellulose gel (F3). The formulations were administered via rectal route in six healthy male adult volunteers. The bioavailability of the three suppository formulations was compared with the oral bioavailability of salbutamol sulfate 2mg tablets (F4). Six volunteers participated in a four-way crossover study, where each study was separated from the other by an interval of 1 weak. Venous blood samples of 5 ml were taken immediately before dosing and after predetermined time intervals of 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 and 8 h. The result showed that Cmax +/- S.D. observed were 12.96 +/- 2.11, 14.78 +/- 2.33, 10.02 +/- 1.42 and 11.51 +/- 1.22 ng ml(-1) for F1, F2, F3 and F4, respectively. The Tmax +/- S.D. were found to be 1.91 +/- 0.20, 1.83 +/- 0.26, 2.50 +/- 0.00 and 2.67 +/- 0.24 h for F1, F2, F3 and F4, respectively. AUC +/- S.D. values were 40.25 +/- 1.88, 42.16 +/- 1.55, 28.62 +/- 1.98 and 37.63 +/- 1.44 ng h per ml for F1, F2, F3 and F4, respectively. The relative bioavailabilities of the investigated formulations were 112.04, 106.96 and 76.06 for formula F2, F1 and F3, respectively, when compared with the oral preparation (F4). The finding indicates that the bioavailability of salbutamol sulfate can be enhanced by delivering it rectally with Suppocire NA base containing 6% Eudispert gel or with Witepsol W25 base containing 3% methyl cellulose to match that of oral tablets. Salbutamol sulfate can be rectally administered in patients who are less compliant with the oral administration.

Purpose. To prepare and evaluate a suppository dosage form of salbutamol sulfate. The prepared formulae with and without different concentrations of gels were tested for hardness, melting time, content uniformity, and drug release. The stability of some of the selected formulae was assessed. Methods. Salbutamol sulfate was formulated as a rectal suppository with emulsifying fatty bases (suppocire and witepsol) and water-soluble bases (PEG) adopting the molding from a melt technique. Physical characteristics and dissolution profiles of the prepared formulations were determined as the responses. The effects of adding gels, methyl cellulose (MC), and Eudispert (Eud) and their concentrations (1, 3, and 6%) on these responses were also investigated. Formulations showing high rank order were scaled up for shelf-life stability study for one year. Results. The results showed that all the investigated formulae have acceptable physical characteristics with respect to hardness, melting time (except F7), and uniformi...

The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The system was made by film coating using Eudragit S100- based formula over the sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid formula was composed mainly of Gelucire 33/01 (G33) with different ratios of surfactants (1-10%). The efficiency of the prepared system was evaluated in vitro for its ability to withstand both the gastric and intestinal medium. In addition, the drug plasma concentrations were monitored after single administration to Beagle dogs and compared to that obtained after administration of a reference marketed, generic, sustained-release TPH tablets, Avolen(®) SR. It was found that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The film-coated capsules showed complete resistance to both the acidic environment (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37°C. In vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the marketed formula followed by sudden increase in TPH blood levels, which recommends the high potential of this system as a chronotherapeutic drug delivery for nocturnal asthma. The prepared PCDCs exhibited a significantly higher C(max) and T(max) and a nonsignificantly different AUC compared with Avolen(®) SR. Higher TPH blood levels from 1 to 8 hours postadministration was detected in the case of the prepared PCDCs.

Garlic contains many sulfhydryl compounds that act as antioxidants. However, the role of nitric oxide (NO) in inflammation is controversial. The aim of the present study is to investigate the possible protective effect of garlic against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of L-arginine (NO precursor) on garlic activity. Intra-rectal inoculation of rats with 4% acetic acid for 3 consecutive days caused a significant increase in the colon weight and marked decrease in the colon length. In addition, acetic acid induced a significant increase in serum levels of nitrate as well as colonic tissue content of malondialdehyde (MDA). Moreover, colonic tissue contents of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were markedly reduced. On the other hand, pre-treatment of rats with garlic (0.25 g/kgbwt, orally) for 4 consecutive weeks and 3 days during induction of colitis significantly reduced the increase in the colon weight induced by acetic acid and ameliorated alterations in oxidant and antioxidant parameters. Interestingly, oral co-administration of garlic (0.25 g/kgbwt) and L-arginine (625 mg/kgbwt) for the same period of garlic administration mitigated the changes in both colon weight and length induced by acetic acid and increased garlic effect on colon tissue contents of MDA and GSH. In conclusion, L-arginine can augment the protective effect of garlic against ulcerative colitis; an effect that might be mainly attributed to its NO donating property resulting in enhancement of garlic antioxidant effect. Further studies will be needed to determine which one of the active ingredients of garlic has the main antioxidant effect to be used with L-arginine.

Vitamin A self-nanoemulsifying drug delivery system (SNEDDS), which comprises soybean oil, Cremophor EL, and Capmul MCM-C8, was prepared and mixed with different grades of Avicel to produce homogenized powders. The resultant powders were compressed into tablets. The prepared tablets were characterized for their thickness, hardness, friability, disintegration time, and dissolution rate. In addition, the relative bioavailability of the tablets in comparison to solid-state Vitamin A oily solution (SSVAOS) tablets was investigated in rats. Vitamin A dissolution rate was markedly different from one formulation to another. From the bioavailability data, it was observed that Vitamin A SNEDD tablets have higher bioavailability (relative bioavailability 143.68%) compared with SSVAOS tablets. The AUC and C(max) of Vitamin A SNEDD tablets were found to be significantly different from that of SSVAOS tablets.

The purpose was to prepare, characterize, and optimize a self-nanoemulsified drug delivery system (SNEDDS) of a model lipophilic compound, all-trans-retinol acetate. As part of the optimization process, the main effects, interaction effects, and quadratic effects of the formulation ingredients were investigated.A three-factor, three-level Box-Behnken design was used to explore the quadratic response surfaces and construct a second-order polynomial model in the form: Y = A + A1X1 + A2X2+ A3X3 + A4X1X2 + A5X2X3 + A6X1X3+ A7X1(2) + A8X2(2) + A9X3(2) + E. Amount of added oil (X1), surfactant (X2), and cosurfactant (X3) were selected as the factors. Particle size (Y1), turbidity (Y2), and cumulative amount of the active ingredient emulsified after 10 (Y3) and 30 (Y4) min were the observed variables. Response surface plots were used to demonstrate the effect of factors (X1), (X2), and (X3) on the response (Y4). Amount of added soybean oil (X1), Cremophor EL (X2), and Capmul MCM-C8 (X3) showed a significant effect on the emulsification rates, as well as on the physical properties of the resultant emulsion (particle size and turbidity). Observed and predicted values of Y4 obtained from the constructed equations were in close agreement. Response surface methodology was then used to predict the levels of factors X1, X2, and X3 under the constrained variables for an optimum response. Applied constraints were 0Y10.5, 1Y220, 60Y380, and 90Y4100. The predicted values were 0.0704 microm for particle size (Y1), 18.95 NTU for turbidity (Y2), 88.88% for drug release after 10 min (Y3), and 110.7% drug release after 30 min (Y4). Two new formulations were prepared according to the predicted levels. The observed and predicted values were in close agreement.

The objectives of the present study were (1) to model the effects of process and formulation variables on in vitro release profile of a model drug dyphylline from multi-particulate beads coated with starch acetate (SA); (2) to validate the models using R2 and lack of fit values; (3) to optimize the formulation by response surface methodology (RSM); (4) to characterize the optimized product by thermal, X-ray and infrared spectroscopic analyses. Dyphylline loaded inert beads were coated using organic solution of SA with high degree of substitution. A three-factor, three-level Box-Behnken design was used for the optimization procedure with coating weight gain (X1), plasticizer concentration (X2) and curing temperature (X3) as the independent variables. The regression equation generated for Y5 (cumulative percent drug released after 12 h) was Y5 = 89.83-11.98X1 + 2.82X2 - 4.31X1(2) + 1.90X1X2. Optimization was done by maximizing drug release in 12 h and placing constraints at dissolution time points of 0.5, 1, 4 and 8 h. The drug release data of the optimized product were close to that predicted by the model. The models could explain 99% of variability in responses. Thermal, X-ray and infrared analyses suggested absence of any significant interaction of the drug with the excipients used in the formulation. SEM photographs showed the integrity of the coating layer.

To prepare and evaluate a suppository dosage form of salbutamol sulfate. The prepared formulae with and without different concentrations of gels were tested for hardness, melting time, content uniformity, and drug release. The stability of some of the selected formulae was assessed.Salbutamol sulfate was formulated as a rectal suppository with emulsifying fatty bases (suppocire and witepsol) and water-soluble bases (PEG) adopting the molding from a melt technique. Physical characteristics and dissolution profiles of the prepared formulations were determined as the responses. The effects of adding gels, methyl cellulose (MC), and Eudispert (Eud) and their concentrations (1, 3, and 6%) on these responses were also investigated. Formulations showing high rank order were scaled up for shelf-life stability study for one year.The results showed that all the investigated formulae have acceptable physical characteristics with respect to hardness, melting time (except F7), and uniformity of drug content. The amount of drug dissolved in 100 min of dissolution time was inversely affected by the melting point of the fatty base. The release from PEG bases was found to be molecular weight dependent. Addition of 1% MC or Eud gel increased the release from all the investigated formulae. Increasing gel concentration to 3% then to 6% showed different effects on the release. The degradation of salbutamol sulfate in the investigated formulae was found to be a first-order reaction.Rectal suppository of salbutamol sulfate could be prepared as an alternative to the oral dosage form to circumvent the first-pass metabolism.