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The healing of a burn wound is a complex process that includes the re-formation of injured tissues and the control of infection to minimize discomfort, scarring, and inconvenience. The current investigation’s objective was to develop and optimize a geranium oil–based self-nanoemulsifying drug delivery system loaded with pravastatin (Gr-PV-NE). The geranium oil and pravastatin were both used due to their valuable anti-inflammatory and antibacterial activities. The Box–Behnken design was chosen for the development and optimization of the Gr-PV-NE. The fabricated formulations were assessed for their droplet size and their effects on the burn wound diameter in experimental animals. Further, the optimal formulation was examined for its wound healing properties, antimicrobial activities, and ex-vivo permeation characteristics. The produced nanoemulsion had a droplet size of 61 to 138 nm. The experimental design affirmed the important synergistic influence of the geranium oil and pravastatin for the healing of burn wounds; it showed enhanced wound closure and improved anti-inflammatory and antimicrobial actions. The optimal formulation led to a 4-fold decrease in the mean burn wound diameter, a 3.81-fold lowering of the interleukin-6 serum level compared to negative control, a 4-fold increase in the inhibition zone against Staphylococcus aureus compared to NE with Gr oil, and a 7.6-fold increase in the skin permeation of pravastatin compared to PV dispersion. Therefore, the devised nanoemulsions containing the combination of geranium oil and pravastatin could be considered a fruitful paradigm for the treatment of severe burn wounds.

Kojic acid (KA) is a BCS class II drug having low solubility and high permeability. This study was designed to enhance the aqueous solubility of KA, as well as its dissolution rate and, in turn, bioavailability, by formulating its smart nanocrystals. Nanocrystals of pure KA were formulated by the top-down method under high-pressure homogenization followed by freeze drying. The nanocrystals were evaluated for stability and other physical characteristics, including zeta sizer analysis, DSC, surface morphology, XRD, drug content, solubility, FTIR and in vitro drug release. The KA nanocrystals were found to be stable when kept at exaggerated conditions. The particle size of the nanocrystals was 137.5 ± 1.7, 150 ± 2.8, and 110 ± 3.0 nm for the F1, F2 and F3 formulations, respectively. There was negative zeta potential for all the formulations. The dispersity index was 0.45 ± 0.2, 0.36 ± 0.4 and 0.41 ± 1.5 for the F1, F2 and F3, respectively. The DSC studies showed that there was no interaction between the KA and the excipients of the nanocrystals. The morphological studies confirmed the presence of rough crystalline surfaces on the nanosized particles. XRD studies showed the successful preparation of nanocrystals. The drug content was in the official range of 90 ± 10%. The solubility of KA was significantly (p < 0.05) enhanced in the formulations of its nanocrystals as compared with pure KA powder. The ATR-FTIR studies revealed the presence of functional groups in both KA and KA-loaded nanocrystals, and no interaction was found between them. The nanocrystals released 83.93 ± 1.22% of KA in 24 h. The study concluded that the nanocrystals were successfully formulated using the top-down method followed by high-pressure homogenization. The solubility, as well as the dissolution, of the KA was enhanced, and this could improve the therapeutic effects of KA.

Urticaria affects all age groups of a population. It is triggered by allergens in foods, insect bites, medications, and environmental conditions. Urticaria is characterized by itching, a burning sensation, wheals and flares, erythema, and localized edema. The aim of this study was to develop a polymeric dosage form of ebastine using Carbopol 940 and mixture of span and tween. The emulsion was prepared, the gelling agent was added and the desired emulgel loaded with active drug was formulated. The formulations were subjected to physical stability, pH, viscosity, spreadability, drug content analysis, thermal analysis, in vitro drug release, and in vivo anti-allergic activity in animal model. The formulated emulgel exhibited good physical stability. The pH of the formulation was in the range of 5.2 ± 0.17 to 5.5 ± 0.20 which is suitable for topical application. Insignificant changes (p > .05) were observed in viscosity and spreadability of stored emulgels. The drug content was in the official limit of Pharmacopeia (i.e. 100 ± 10%). DSC measurements predicted that there is no interaction between the active moiety and excipients in emulgel formulation. The optimized formulation (ES3) released 74.25 ± 1.8% of ebastine after 12 h. The ebastine emulgel showed significant (p

Nanoparticles are used increasingly for the treatment of different disorders, including burn wounds of the skin, due to their important role in wound healing. In this study, acriflavine-loaded poly (ε-caprolactone) nanoparticles (ACR-PCL-NPs) were prepared using a double-emulsion solvent evaporation method. All the formulations were prepared and optimized by using a Box–Behnken design. Formulations were evaluated for the effect of independent variables, i.e., poly (ε-caprolactone) (PCL) amount (X1), stirring speed of external phase (X2), and polyvinyl alcohol (PVA) concentration (X3), on the formulation-dependent variables (particle size, polydispersity index (PDI), and encapsulation efficiency) of ACR-PCL-NPs. The zeta potential, PDI, particle size, and encapsulation efficiency of optimized ACR-PCL-NPs were found to be −3.98 ± 1.58 mV, 0.270 ± 0.19, 469.2 ± 5.6 nm, and 71.9 ± 5.32%, respectively. The independent variables were found to be in excellent correlation with the dependent variables. The release of acriflavine from optimized ACR-PCL-NPs was in biphasic style with the initial burst release, followed by a slow release for up to 24 h of the in vitro study. Morphological studies of optimized ACR-PCL-NPs revealed the smooth surfaces and spherical shapes of the particles. Thermal and FTIR analyses revealed the drug–polymer compatibility of ACR-PCL-NPs. The drug-treated group showed significant re-epithelialization, as compared to the controlled group.

On the basis of fungal involvement, rhinosinusitis is categorized into allergic, mycetoma, chronic, and acute invasive types. The aim of the current study was to evaluate the efficacy of an amphotericin gel in situ loaded with nanotransferosomes against Aspergillus flavus, which causes allergic rhinosinusitis. A Box&ndash, Behnken design was utilized to study the interaction among the nanotransferosomes and optimize independent variables in formulating them, in order to match the prerequisites of selected responses. The optimal formulation was determined to be 300 mg/mL soybean lecithin, 200 mg/mL amphotericin B (AMP), and 150 mg/mL clove oil, resulting in a particle size of 155.09 nm, 84.30% entrapment efficacy (EE), inhibition zone of 16.0 mm, and 0.1197 mmol serum creatinine. The optimized batch was further prepared into an in situ gel and evaluated for various parameters. The optimized formulation released 79.25% AMP and enhanced permeation through the nasal membrane, while the other formulations did not achieve complete absorption. According to in vivo tests using rabbits as animal models, the optimized AMP-nanotransferosomal formulations (NT) in in situ gel result in a non-significant difference among the various kidney function parameters. In conclusion, nasal in situ gel loaded with AMP-clove oil nanotreansfersomes can act as a promising novel carrier that enhances antifungal activity and decreases AMP nephrotoxicity.

Acne vulgaris is a common skin disease that affects everybody at least once in their lives. The treatment is challenging because the stratum corneum contains rigid corneocytes surrounded by intercellular lamellae that are difficult to bypass. In the present study, we intended to formulate an effective nanoemulsion that could deliver isotretinoin (ITT) with enhanced solubility, permeability, and bioavailability across the skin. ITT can have a serious hepatotoxic effect if given too frequently or erratically. Therefore, to overcome the aforesaid limitation, quercetin (QRS), a hepatoprotective agent, was incorporated into the formulation. Initially, the ITT solubility was determined in various surfactants and cosurfactants to select the essential ingredients to be used in the formulation and to optimize a nanoemulsion that could enhance the solubility and permeability of ITT and its antimicrobial activity against Staphyloccocus aureus, which is the main microorganism responsible for acne vulgaris. The mixture design was applied to study the interactions and optimize the independent variables that could match the prerequisites of selected dependent responses. A formulation containing 0.25 g of rosehip oil, 0.45 g of surfactant (Lauroglycol-90), and 0.3 g of cosurfactant (propylene glycol) was chosen as an optimized desirable formulation. The optimized batch was loaded with QRS and evaluated for in vitro and ex vivo permeation. The in vivo hepatotoxicity was assessed through topical administration. Permeability studies confirmed the enhanced permeation percentage of ITT (52.11 &plusmn, 2.85%) and QRS (25.44 &plusmn, 3.18%) of the optimized formulation, with an enhanced steady-state flux (Jss). The in vivo studies conducted on experimental animals demonstrated superior hepatoprotective activity of the prepared optimized formulation compared with other formulations of drugs and commercially marketed products. We anticipate that this optimized ITT formulation, followed up with good clinical evaluations, can be a breakthrough in the safe treatment of acne vulgaris.

Natural polymers are revolutionizing current pharmaceutical dosage forms design as excipient and gained huge importance because of significant influence in formulation development and drug delivery. Oral health refers to the health of the teeth, gums, and the entire oral-facial system that allows us to smile, speak, and chew. Since years, biopolymers stand out due to their biocompatibility, biodegradability, low toxicity, and stability. Polysaccharides such as cellulose and their derivatives possess properties like novel mechanical robustness and hydrophilicity that can be easily fabricated into controlled-release dosage forms. Cellulose attracts the dosage design attention because of constant drug release rate from the precursor nanoparticles. This review discusses the origin, extraction, preparation of cellulose derivatives and their use in formulation development of nanoparticles having multidisciplinary applications as pharmaceutical excipient and in drug delivery, as bacterial and plant cellulose have great potential for application in the biomedical area, including dentistry, protein and peptide delivery, colorectal cancer treatment, and in 3D printable dosage forms.

Trichophyton rubrum (T. rubrum) is the main cause of chronic dermatophytosis which is highly prevalent worldwide. This study was aimed to fabricate and characterize polymeric emulgel of eugenol and linalool for the treatment of T. rubrum infections. Using the slow emulsification method, the emulgel was prepared and characterized for thermodynamic stability, pH analysis, viscosity, spreadability, swelling behavior, %drug content, surface morphology, globules size, polydispersity index, surface charge (mV), thermal behavior, in vitro drug release and XRD studies. Biological activities of emulgel were conducted against T. rubrum in vitro and in vivo. Results indicated that emulgel formulations were thermodynamically stable. The pH of the formulations was within an acceptable range for skin. The viscosity and spreadability were optimum for the better patient compliance. The swelling behavior was 111.10 ± 1.25% after 90 min. The drug content was within the official pharmacopeia limit i.e., 100 ± 10%. The surface morphology revealed by scanning electron microscopy showed a spherical-shaped structure with characteristic larger cracks and wrinkles. The droplet size, PDI, and surface charge of the optimized emulgel were 888.45 ± 8.78 nm, 0.44 and −20.30 mV, respectively. The emulgel released 84.32% of eugenol and 76.93% of linalool after 12 hr. There was complete disappearance of the diffraction peaks corresponding to the drugs after XRD analysis. In rabbits, the infection was safely and completely recovered after 12 days and the emulgel produced significant effects (p &lt, 0.05) similar to the standard product Clotrim®. It is concluded that the eugenol–linalool emulgel best described all its physical properties and can be applied topically for the treatment of T. rubrum infections.

Trichophyton rubrum (T. rubrum) is the main cause of chronic dermatophytosis which is highly prevalent worldwide. This study was aimed to fabricate and characterize polymeric emulgel of eugenol and linalool for the treatment of T. rubrum infections. Using the slow emulsification method, the emulgel was prepared and characterized for thermodynamic stability, pH analysis, viscosity, spreadability, swelling behavior, %drug content, surface morphology, globules size, polydispersity index, surface charge (mV), thermal behavior, in vitro drug release and XRD studies. Biological activities of emulgel were conducted against T. rubrum in vitro and in vivo. Results indicated that emulgel formulations were thermodynamically stable. The pH of the formulations was within an acceptable range for skin. The viscosity and spreadability were optimum for the better patient compliance. The swelling behavior was 111.10 ± 1.25% after 90 min. The drug content was within the official pharmacopeia limit i.e., 100 ± 10%. The surface morphology revealed by scanning electron microscopy showed a spherical-shaped structure with characteristic larger cracks and wrinkles. The droplet size, PDI, and surface charge of the optimized emulgel were 888.45 ± 8.78 nm, 0.44 and −20.30 mV, respectively. The emulgel released 84.32% of eugenol and 76.93% of linalool after 12 h. There was complete disappearance of the diffraction peaks corresponding to the drugs after XRD analysis. In rabbits, the infection was safely and completely recovered after 12 days and the emulgel produced significant effects (p < 0.05) similar to the standard product Clotrim®. It is concluded that the eugenol–linalool emulgel best described all its physical properties and can be applied topically for the treatment of T. rubrum infections.

Background Ibuprofen (IB) is a potent non-steroidal anti-inflammatory drug but of limited use due to low solubility and gastric ulceration side effect. Objective To utilize pumpkin seed oil in the form of self nanoemulsion delivery system (SNEDs) as an enhancer for ibuprofen solubility, and a protective factor against ibuprofen-induced peptic ulcer. Method Pseudo-ternary phase diagrams were utilized to determine the self-emulsifying region. The effects of formulation variables, i.e., concentrations of pumpkin oil (X1), polyethylene glycol-40 stearate (MYS-40MV) as a surfactant (X2), and polyethylene glycol-60 hydrogenated castor oil (HCO-60) as cosurfactant, on globule size and anti-ulcerative activity were evaluated. Results Optimum levels of IB-SNEDs components indicated by mixture design were X1(26.5%), X2(63.5%), and X3(10%), respectively. The optimized formula showed globule size of 104 nm. The anti-ulcerative activity score of the optimized formulation was 0.5, indicating a potential anti-ulcerative effect result from incorporation of pumpkin oil as one of IB-SNEDS component, in comparison to score 4 and 5 for the marketed product, and formulation containing oleic acid as an oil, respectively. Conclusion Pumpkin seed oil-based SNEDS enhanced the solubility and protected against ulceration effect of ibuprofen. The study suggests that pumpkin seed oil can effectively address the limitation of ibuprofen-induced gastric ulcer.

Objective: Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs). Significance: Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension. Methods: Plackett-Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method. The investigated variables were initial drug load (X1), chitosan percentage (X2), tripolyphosphate sodium (TPP) percentage (X3), poloxamer percentage (X4), homogenization speed (X5), homogenization time (X6) and TPP addition rate (X7). The prepared DM-loaded NPs have been fully evaluated for particle size (Y1), Zeta potential (Y2), production yield (Y3), entrapment efficiency (Y4), loading capacity (Y5), initial burst (Y6), and cumulative drug release (Y7). Finally, DM pharmacokinetic has been investigated on healthy albino male rabbits by means of non-compartmental analysis. Results: The combination of variables showed variability of Y1, Y2, and Y3 equal to 122-710 nm, 3.49-23.63 mV, and 47.31-92.96%, respectively. While Y4 and Y5, reached 99.87%, and 8.53%, respectively. The prepared NPs revealed that X2, X3, and X4 are the variables that play the important role in controlling the release behavior of DM from the NPs. The in vivo pharmacokinetic results indicated the enhancement in bioavailability of DM by 7 folds compared to drug suspension and the mean residence time prolonged to 23.72 h compared to 4.7 h of drug suspension. Conclusion: The study proved that controlling the release of DM from NPs enhance its bioavailability and improve the compliance of patients with hypertension or benign prostatic hyperplasia.

Khaled Hosny,1– 3 Hani Asfour,4 Waleed Rizg,1– 3 Nabil A Alhakamy,1– 3 Amal Sindi,5 Hala Alkhalidi,6 Walaa Abualsunun,1 Rana Bakhaidar,1 Alshaimaa M Almehmady,1 Sara Akeel,5 Sarah Ali,5 Adel Alghaith,7 Sultan Alshehri,7 Rasha Khallaf8 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 5Oral diagnostic sciences department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Clinical pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62511, EgyptCorrespondence: Khaled HosnyDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaTel +966 561682377Email elswaify2000@yahoo.com; kmhomar@kau.edu.saIntroduction: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation’s aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health.Methods: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities.Results: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats.Conclusion: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.Keywords: oregano essential oil, nanoemulsion, Box‒Behnken design, ulcer index, required HLB, carvacrol, thymol, stability index

Maintaining oral health helps to prevent periodontal inflammation and pain, which can progress into more detrimental issues if left untreated. Meloxicam (MX) is a commonly used analgesic for periodontal pain, but it can have adverse gastrointestinal effects and poor solubility. Therefore, this study aimed to enhance the solubility of MX by developing a self-nanoemulsifying drug delivery system (SNEDDS). Considering the anti-ulcer activity of peppermint oil (PO), it was added in a mixture with medium-chain triglyceride (MCT) to the MX-loaded SNEDDS formulation (MX-PO-SNEDDS). After optimization, MX-PO-SNEDDS exhibited a PO:MCT ratio of 1.78:1, surfactant mixture HLB value of 14, and MX:oil mix ratio of 1:15, a particle size of 47 ± 3 nm, stability index of 85 ± 4%, ex vivo Jss of 4 ± 0.6 μg/cm2min, and ulcer index of 1 ± 0.25 %. Then, orally flash disintegrating lyophilized composites (MX-SNELCs) were prepared using the optimized MX-PO-SNEDDs. Results reveal that MX-SNELCs had a wetting time of 4 ± 1 s and disintegration time of 3 ± 1 s with a high in vitro MX release of 91% by the end of 60 min. The results of pharmacokinetic studies in human volunteers further demonstrated that, compared to a marketed MX tablets, MX-SNELCs provided a higher Cmax, Tmax, and AUC and a relatively greater bioavailability of 152.97 %. The successfully developed MX-SNELCs were found to be a better alternative than the conventional tablet dosage form, thus indicating their potential for further development in a clinically acceptable strategy for managing periodontal pain.

The majority of newly developed drugs need to be incorporated with delivery systems to maximize their effect and minimize side effects. Nanoemulsions (NEs) are one type of delivery system that helps to improve the solubility and dissolution of drugs, attempting to enhance their bioavailability and onset of action. The objective of this investigation was to develop an omega-3 oil-based NE loaded with loxoprofen (LXP) to enhance its dissolution, in vitro release, and mucosal penetration and decrease its mucosal ulcerative effects when applied in an oral treatment. LXP-loaded NEs were formulated with varying levels of omega-3 oil (10–30%), surfactant polyoxyethylene-C21-ethers (laureth-21) (40–60%), and co-surfactant polyethylene glycol-40 hydrogenated castor oil (HCO-40) (30–50%) using an extreme vertices mixture design. The developed NEs were characterized for globule size and drug loading capacity. The optimal formulation was tested for in vitro drug release, ex vivo permeation, and ulcer index value. The developed NE acquired a globule size ranging 71–195 nm and drug loading capacity of 43–87%. Considering the results of the in vitro release study, the optimized NE formulation achieved 2.45-fold and 2-fold increases in drug permeation across tested mucosa compared to a marketed tablet and drug aqueous dispersion, respectively. Moreover, the optimum NE exhibited the best ulcer index in comparison to drug aqueous suspension and different formulations when tested in rats. Overall, this research highlights the capacity of NEs to deliver LXP with enhanced solubility, drug release, and permeation while effectively protecting the application site from side effects of the model drug.

Mucoadhesive polymers have an essential role in drug localization and target-specific actions in oral delivery systems. The current work aims to develop and characterize a new mucoadhesive polysaccharide polymer (thiolated xanthan gum-TXG and S-Protected thiolated xanthan gum-STX) that was further utilized for the preparation of repaglinide mucoadhesive tablets. The thiolation of xanthan gum was carried out by ester formation through the reaction of the hydroxyl group of xanthan gum and the carboxyl group of thioglycolic acid. Synthesis of TXG was optimized using central composite design, and TXG prepared using 5.303 moles/L of TGA and 6.075 g/L of xanthan gum can accomplish the prerequisites of the optimized formulation. Consequently, TXG was further combined with aromatic 2-mercapto-nicotinic acid to synthesize STX. TXG and STX were further studied for Fourier-transform infrared spectroscopy, rheological investigations, and Ellman’s assay (to quantify the number of thiol/disulfide groups). A substantial rise in the viscosity of STX might be due to increased interactions of macromolecules liable for improving the mucosal adhesion strength of thiolated gum. STX was proven safe with the support of cytotoxic study data. Mucoadhesive formulations of repaglinide-containing STX showed the highest ex vivo mucoadhesion strength (12.78 g-RSX-1 and 17.57 g- RSX-2) and residence time (>16 h). The improved cross-linkage and cohesive nature of the matrix in the thiolated and S-protected thiolated formulations was responsible for the controlled release of repaglinide over 16 h. The pharmacokinetic study revealed the greater AUC (area under the curve) and long half-life with the RSX-2 formulation, confirming that formulations based on S-protected thiomers can be favorable drug systems for enhancing the bioavailability of low-solubility drugs.

Nanocrystals are carrier-free, submicron-sized, colloidal drug delivery systems with particle sizes in the mean nanometer range. Nanocrystals have high bioavailability and fast absorption because of their high dissolution velocity and enhanced adhesiveness to cell membranes. Loxoprofen, a nonsteroidal anti-inflammatory drug belonging to the Biopharmaceutical Classification System (BCS) II drug class, was selected as the model drug. The aim of this study was to formulate nanocrystals of loxoprofen. A total of 12 formulations (F1 to F12) were prepared. An antisolvent technique was used to determine the effects of various stabilizers and processing conditions on the optimization of formulations. The various stabilizers used were hydroxypropyl methylcellulose (0.5%), polyvinylpyrrolidone (0.5%), and sodium lauryl sulfate (0.1%). The various characterizations conducted for this research included stability studies at 25 °C and 4 °C, scanning electron microscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), zeta potentials, polydispersity indexes, and dissolution studies. F10 was the optimized formulation that showed stability at room temperature, as well as at a refrigerated temperature, for 30 days. A high dissolution rate (100% within the first 10 min) was shown by comparative dissolution studies of nano-suspensions with the micro-suspension and raw loxoprofen. F10 formulation had a non-porous and crystalline morphology on evaluation by TEM and XRPD, respectively, and the average particle size was 300 ± 0.3 nm as confirmed by TEM. DSC recorded a reduction in the melting point (180 °C processed and 200 °C unprocessed melting points). The dissolution rate and solubility of the formulated loxoprofen nanocrystals were significantly enhanced. It can be concluded that selecting suitable stabilizers (i.e., polymers and surfactants) can produce stable nanocrystals, and this can potentially lead to a scaling up of the process for commercialization.

Acne Vulgaris is one of the most common chronic inflammatory skin disorders that affect majority of teen-agers worldwide. Isotretinoin (ITT) is the drug of choice in the management of acne, but, it suffers from serious side-effects including hepatotoxicity, and some psychological disturbances following its oral intake. The objective of this study was to develop and optimize ITT loaded nanoemulsions (ITT-SNEDDS) and to incorporate resveratrol (RSV)in optimum formulation to decrease ITT side effects The ITT solubility was first tested in various essential oils, surfactants, and co-surfactants to select the essential nanoemulsion ingredients. Mixture design was applied to study the effect of independent variables and their interactions on the selected dependent responses. The developed ITT-SNEDDS were characterized for their globule size and ex vivo permeation. The optimized batch was further loaded with RSV and evaluated for in vitro and ex vivo permeation and for in vivo hepatotoxicity. The developed ITT-SNEDDS exhibited globule size below 300 nm, up to 272.27 ± 7.12 mcg/cm2.h and 61.27 ± 2.83% of steady-state flux (JSS) and permeability % respectively. Optimum formulation consisted of 0.15 g oil mixture, 0.6 g of surfactant (Labrasol), and 0.250 g co-surfactant (Transcutol). Permeability studies confirmed the enhanced permeation percentage of ITT (40.77 ± 1.18%), and RSV (29.94 ± 2.02%) from optimized formulation, with enhanced steady-state flux (JSS). In vivo studies demonstrated the superior hepatoprotective activity of optimized formulation compared to a different drug formulations and marketed product. Therefore, RVS loaded ITT-SNEDDS might be a successful strategy for acne management with improved action, and minimum side effects.

Sildenafil citrate is a drug used throughout the world primarily to treat erectile dysfunction. Several problems with the commercially available product decrease its efficacy, such as limited solubility, delayed onset of action, and low bioavailability with a large variability in the absorption profile. This study aimed to develop an optimized self-nanoemulsifying lyophilized tablet for the drug to conquer the foresaid problems. Sildenafil solubility in various surfactants, oils, and cosurfactants was attempted. An optimized formulation of a loaded self-nanoemulsion with a small droplet size was developed by applying a special cubic model of the mixture design. Sixteen formulations were prepared and characterized for droplet size. On the basis of solubility studies, a clove oil/oleic acid mixture, polysorbate 20 (Tween 20), and propylene glycol were selected as the proposed oil, surfactant, and cosurfactant, respectively. On the basis of desirability, an optimized sildenafil citrate-loaded self-nanoemulsifying delivery system containing 10% of the oil mixture, 60% of the surfactant, and 30% of the cosurfactant had a droplet size of 65 nm. Subsequently, the tablet form was fabricated with optimum ratios of 0.4% fumed silica, 0.1% hydroxypropyl methylcellulose, and 0.4% sodium starch glycolate. This formula showed satisfactory results in both disintegration and dissolution studies. In vivo pharmacokinetic studies indicated a higher bioavailability (1.44 times) and rapid absorption profile for the study&rsquo, s tablets compared with commercially available tablets. In conclusion, highly bioavailable oral lyophilized flash tablets of sildenafil were successfully prepared. They will be a good alternative to the conventional solid-dosage form.

Burn wound healing is a complex process that involves the repair of injured tissues and the control of infection to diminish the scar formation, pain, and discomfort associated with such injuries. The aim of this research was to formulate and optimize a self-nanoemulsion drug delivery system based on the use of coconut oil and loaded with simvastatin. Coconut oil possesses antiinflammatory and antibacterial activity, and simvastatin has interesting properties for promoting the wound-healing process because it increases the production of the vascular endothelial growth factor at the site of injury. The Box&ndash, Behnken design was employed for the optimization of the coconut oil&ndash, simvastatin self-nanoemulsion drug delivery system. The prepared formulations were characterized according to globular size and their activity in the healing of burn wounds by assessing the mean wound diameter and level of interlukin-6 in experimental animals. Additionally, the antimicrobial activity of the prepared formulations was assessed. The nanoemulsion was considered adequately formed when it had droplets of between 65 and 195 nm. The statistical design proved the important synergistic effect of coconut oil and simvastatin for burn wound management in their synergistic potentiation of wound closure and their anti-inflammatory and antimicrobial effects. The optimum formulation achieved up to a 5.3-fold decrease in the mean burn wound diameter, a 4.25-fold decrease in interleukin-6 levels, and a 6-fold increase in the inhibition zone against Staphylococcus aureus when compared with different control formulations. Therefore, the designed nanoemulsions containing a combination of coconut oil and simvastatin could be considered promising platforms for the treatment of chronic and burn wounds.

Gout is the most familiar inflammatory arthritis condition caused by the elevation of uric acid in the bloodstream. Febuxostat (FBX) is the latest drug approved by the United States Food and Drug Administration (US FDA) for the treatment of gout and hyperuricemia. FBX is characterized by low solubility resulting in poor gastrointestinal bioavailability. This study aimed at improving the oral bioavailability of FBX by its incorporation into self-nanoemulsifying delivery systems (SNEDS) with minimum globule size and maximum stability index. The SNEDS-incorporated FBX was loaded into a carrier substrate with a large surface area and lyophilized with other excipients to produce a fluffy, porous-like structure tablet for the transmucosal delivery of FBX. The solubility of FBX was studied in various oils, surfactants, and cosurfactants. Extreme vertices design was utilized to optimize FBX-SNEDS, and subsequently loaded into lyophilized tablets along with suitable excipients. The percentages of the main tablet excipients were optimized using a Box&ndash, Behnken design to develop self-nanoemulsifying lyophilized tablets (SNELTs) with minimum disintegration time and maximum drug release. The pharmacokinetics parameters of the optimized FBX-SNELTs were tested in healthy human volunteers in comparison with the marketed FBX tablets. The results revealed that the optimized FBX-SNELTs increased the maximum plasma concentration (Cmax) and decreased the time to reach Cmax (Tmax) with a large area under the curve (AUC) as a result of the enhanced relative oral bioavailability of 146.4%. The significant enhancement of FBX bioavailability is expected to lead to reduced side effects and frequency of administration during the treatment of gout.

Bifonazole (BF) is a highly lipophilic antifungal drug that has limited absorption. A self-nano-emulsifying drug delivery system (SNEDDS) not only aids solubility, but it also enhances the absorption. The aim was to formulate BF-SNEDDS for topical delivery using the mixture design and to evaluate the antifungal activity, permeability, and in-vivo pharmacokinetics. Solubility of BF in different oils, surfactants, and cosurfactants was evaluated. A mixture design was used to optimize the formulation variables, X1 (Peceol% as oil), X2 (Kolliphore % as a surfactant), and X3 (Plurol Oleique% as cosurfactant), to evaluate their effects on the globule size. Antifungal activity against Candida albicans, and ex-vivo permeability across rat abdominal membrane were evaluated. The in-vivo pharmacokinetics was also assessed. Results of mixture design indicated that the optimum levels for SNEDDs components were X1(15%), X2(65%), and X3(20%). The globule size, the zone of inhibition, and permeability coefficient for the optimized formula were 36 ± 3 nm, 26 ± 3 mm, and 7.3 × 10−4 cm/min, respectively. This results indicated that, the optimum formula enhances the antifungal activity, ex vivo permeability, and in vivo bioavailability by 1.85-fold, 2.179-fold, and 6-fold, respectively, compared to aqueous suspension. In conclusion, BF-SNEDDS had enhanced anti-fungal pharmacotherapy and acts as a promising medium for transdermal delivery.

Mefenamic acid (MA) is a non-steroidal anti-inflammatory drug with analgesic activity. Marketed MA tablets or capsules often result in gastrointestinal disorders, such as upset and bleeding. MA also has poor solubility and short half-life (2 h), which requires frequent dosing, leading to higher incidence of side effects. The objective was to develop a statistically optimized nanoethosome (NE) formulation of MA loaded into transdermal films, as an alternative to oral delivery, to offer an extended release behavior. Box-Behnken design was used to analyze the effect of phospholipid concentration, ethanol concentration, and ultrasonication time. On three variables, particle size, entrapment efficiency, and steady state flux. Optimized MA-loaded nanoethosome formulation was prepared using a thin layer evaporation technique. Further, the nanoethosomal-loaded transdermal film was evaluated for in-vitro release, ex-vivo permeation, and in-vivo pharmacokinetics studies. The optimized formula indicated particle size of 97 nm with 80% of entrapment efficiency. Enhanced skin permeation of MA was more than 3.4 folds higher for nanoethosomes loaded films in comparison to pure drug transdermal films The estimated steady state flux was 2 and 15 mcg/cm2 min. The bioavailability studies indicated that mean AUC0-48 increased by 4-folds after transdermal delivery of optimized nanoethosomal film with no side effects.

Vancomycin is a broad-spectrum antibiotic. However, its use is limited by nephrotoxicity. The aim of this research was to utilize nanotechnology to exert a protective effect from the nephrotoxicity of Vancomycin by developing Vancomycin loaded solid lipid nanoparticles (SLN) with an antioxidant Ellagic acid. A solvent evaporation-ultrasonication technique was used in the formulation of the SLN, and the prepared nanoparticles were characterized for particle size, entrapment efficiency, and stability. Moreover, an in vivo study was performed on rabbits to assess the protective effect of Ellagic acid on occurrence of Vancomycin nephrotoxicity. The results indicated that Vancomycin-Ellagic acid SLNs were successfully prepared with a size of 164 nm, zeta potential of 14.2 mV, and entrapment efficiency for Vancomycin and Ellagic acid at 35.6 and 94.8, respectively. The in vivo test indicated a non-significant difference between levels of all tested kidney function parameters, comprised of: serum creatinine, urea, glucose, calcium, sodium, and potassium, for animals treated with Vancomycin-Ellagic acid SLNs and a control group. In comparison, the group treated with Vancomycin alone showed a significant difference in all tested parameters from the control group. Conclusion Vancomycin-ellagic SLNs act as a promising novel carrier that decreases Vancomycin nephrotoxicity, and exerts an antioxidant protective effect from kidney failure.

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE7 β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

Allopurinol (ALP) is the most extensively used drug for lowering blood urate concentrations and thereby decreasing the number of repeated attacks of gout. Despite being a potent drug, ALP suffers from poor oral bioavailability and dose-related nephrotoxicity. Therefore, the current study was designed with the objectives to improve the drug's pharmacokinetics and enhance its renal clearance. For this purpose, a renal protective agent, i.e., thioctic acid (THA), was coadministered with ALP through the optimized ALP-THA-loaded nanostructured lipid carrier (ALP-THA NLC). A face-centered central composite experimental design was implemented for the development of an optimized NLC. Fabricated ALP-THA NLCs were characterized according to particle size and entrapment efficiency. The optimized NLC had a particle size of 70 nm and a percentage of entrapment of 94%. After 12 h of in vitro release study, 74% of the drug was released from NLC, whereas 66% and 60% of the drug was released from the aqueous suspension and tablet, respectively. In addition, the cumulative amount of ALP permeated the intestinal barrier from the optimized NLC, aqueous suspension, and tablet was 1850 ± 211 μg/cm2, 910 ± 350 μg/cm2, and 760 ± 406 μg/cm2, respectively. Hence, the in vitro release and ex vivo permeation study demonstrated more favorable outcomes for the optimized ALP-THA NLC than aqueous suspension or commercially available tablets containing ALP. The in vivo nephrotoxicity study showed that the THA present in ALP-THA NLC restored normal renal function and eliminated the nephrotoxicity associated with ALP. Thus, it can be concluded that a novel optimized ALP-THA NLC could be a vernal scaffold for treating gout.

Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP).Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients.Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products.Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6-7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4 ng/mL), longer time to reach maximum plasma concentration (4 h) and longer tMatrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles.

Owing to its limited aqueous solubility, Phytomenadione (vitamin K) undergoes a low bioavailability (50%) with a large inter-individual variability after oral administration. Therefore, the aim of this work was to incorporate vitamin K into nanostructure lipid carrier systems to improve its aqueous solubility and bioavailability. Phytomenadione was used as a liquid lipid; Precirol ATO5, and Compritol ATO were used as solid lipids; Labrasol and Cremophore EL as water soluble surfactants; Capryol 90 and Lauroglycol as lipid soluble surfactants. Eight formulas were prepared and characterized for their particle sizes, zeta potential, entrapment efficiencies, and drug release. Those formulas had particle sizes ranging from 25.4 to 68.3 nm. The best formula, consisting of 15% Phytomenadione, 45% Precirol ATO5, 30% Cremophore EL, and 10% Lauroglycol 90, was selected for stability study and characterized by the techniques mentioned above and scanning electron microscopy. It had the highest drug loading and an acceptable in vitro release profile (94.54% within 30 min). This formula was also chemically and physically stable, and it recorded a relative bioavailability of 645.5% in rabbits compared to the commercial conventional tablet. This formula could be a promising carrier regarding its ease of preparation, dosage form versatility and enhanced bioavailability.

Rotigotine is a non-ergoline, high lipophilic dopamine agonist. It is indicated as the first-line therapy for Parkinson's disease (PD) and Restless Leg Syndrome (RLS). However, the precise mechanism of rotigotine is yet to be known. Rotigotine has similar safety and tolerability to the other oral non-ergolinic dopamine antagonists in clinical trials, which include nausea, dizziness and somnolence. Neupro® was the first marketed transdermal patch formulation having rotigotine. The transdermal delivery system is advantageous as it enables continuous administration of the drug, thus providing steady-state plasma drug concentration for 24-hours. Intranasal administration of rotigotine allows the drug to bypass the blood-brain barrier enabling it to reach the central nervous system within minutes. Rotigotine can also be formulated as an extended-release microsphere for injection. Some challenges remain in other routes of rotigotine administration such as oral, parenteral and pulmonary, whereby resolving these challenges will be beneficial to patients as they are less invasive and comfortable in terms of administration. This review compiles recent work on rotigotine delivery, challenges and its future perspective.

Khaled M Hosny Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Khaled M HosnyDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaTel +966561682377Email elswaify2000@yahoo.comBackground: Saquinavir mesylate (SQR) tablets are widely used against human immunodeficiency virus. SQR has bioavailability issues owing to its poor aqueous solubility, extensive first-pass metabolism, and even low gastrointestinal tract permeability and absorption.Objective: An in-depth optimization process was carried out using factorial design to improve the permeation parameters and thereby the bioavailability of SQR by formulating self-nanoemulsifying drug delivery system (SNEDDS)-loaded polymeric transdermal films.Methods: The solubility of SQR in different nanoemulsion components was examined. Various combinations of selected components were prepared in an extreme vertices mixture design to identify the useful nanoemulsion zone and to develop SNEDDS with minimum globule size. The optimized SQR-SNEDDS was loaded in polyvinyl alcohol (PVA)-based transdermal films. The Box-Behnken design was used to optimize and evaluate SQR permeability. The prepared films were characterized for thickness, tensile strength, elongation, folding endurance, and accelerated stability studies. The optimized film was examined for ex vivo skin permeation and in vivo pharmacokinetic parameters.Results: The optimized SQR-SNEDDS was prepared in proportions of 0.1, 0.55, and 0.35 of clove oil, labrasol, and Transcutol, respectively. The implemented Box-Behnken design indicated the optimized film consisted of 1.0% PVA, 0.25% propylene glycol, and clove oil as the oil phase. The tensile strength, thickness, percent elongation, and folding endurance of the optimized SQR-SNEDDS film were 0.93 ± 0.013 kg/cm2, 0.22 ± 0.006 mm, 43.1 ± 0.022%, and >200 times, respectively. A higher Cmax and double the AUC were observed for SQR-SNEDDS–loaded film in comparison to pure SQR-loaded films.Conclusion: Implementation of a two-step design to optimize and control experimental factors in the preparation of SQR-SNEDDS and its loading onto PVA-based transdermal films was achieved. The films indicated improved ex vivo skin permeation, enhanced bioavailability, and overcame the limitations of the oral dosage form.Keywords: saquinavir, human immunodeficiency virus, bioavailability, factorial design, self-nano emulsifying drug delivery system, transdermal films

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.

Conventional treatments for common disorders of the oral mucous membranes have great challenges, and this has motivated the development of local therapeutics with an advanced delivery platform. The present study aimed to develop a hydrogel containing clotrimazole‒rosehip oil nanoethosomes (CZ-RO-NE) and to evaluate its antibacterial and antifungal efficacy and ulcer index. Optimization of CZ-RO-NE was performed by the Box‒Behnken statistical design using l -α-phosphatidylcholine, CZ, and RO as independent variables. The optimized formulations were characterized for their rheological properties, in vitro release characteristics, and ex vivo permeability. An optimized formulation was fabricated using the thin-layer evaporation technique where the rheological property indicated non-Newtonian flow. The in vitro release profile of the formulations showed a significantly higher release (80 ± 6.723%) from the CZ-RO-NE‒embedded hydrogel compared with the marketed formulation and drug suspension (p

In patients suffering liver damage, the gut microbiota and their metabolic products are reported to be the key factors in the worsening of associated psychiatric and neurological conditions. In particular, the increased production of ammonia resulting from microbial activities in the gut is considered one of the important factors that lead to the development of hepatic coma. The use of neomycin, an antimicrobial that has been approved by the United States Food and Drug Administration, in the treatment of hepatic coma is restricted because its therapeutic use is often accompanied by severe toxicities (e.g., nephrotoxicity). The present study aims to optimize the development of a neomycin-loaded self-nanoemulsifying drug delivery system using a statistical design into which thioctic acid is incorporated (NM-TH-SNEDDS). Thioctic acid has a well-established antioxidant efficacy, which in turn reduces the nephrotoxic effect of neomycin in patients, and also has a significant hepatoprotective role. The Box–Behnken design of statistical analysis was performed to optimize the formulations. The optimized formula showed 150 nm globule size, 592 μg of thioctic acid permeated, microbiological activities enhanced 12 times, and ameliorative properties of the formulation in terms of renal function parameters were enhanced according to the results of serum creatinine measurement. Overall, it could be concluded that the NM-TH-SNEDDS formulated using eucalyptus oil would be a suitable platform for the treatment of hepatic coma, with enhanced efficacy and safety. The findings of the present study need to be explored in detail to gain further insights that could influence the direction of future clinical research.

Azacitidine (AZA), an inhibitor of DNA methyltransferase, is a commonly recognized drug used in clinical treatment for myelodysplastic syndrome and breast cancer. Due to higher aqueous solubility and negative log P of AZA causes poor cancer cell permeation and controlled release. The objective of the present study was to formulate and optimize AZA-loaded liposome (AZA-LIPO) for breast cancer chemotherapy by using Box Behnken design (BBD) and in vitro evaluation using MCF-7 cells. AZA-LIPO were prepared using a thin film hydration technique and characterization study was performed by using FTIR and DSC. The prepared formulations were optimized using BBD and the optimized formulation was further subjected for particle size, surface charges, polydispersity index (PDI), drug loading, entrapment efficiency, TEM, XRD, in-vitro drug release and hemolytic toxicity. The mean particle size of optimized AZA-LIPO was 127 nm. Entrapment efficiency and drug loading of AZA-LIPO was found to be 85.2% &plusmn, 0.5 and 6.82 &plusmn, 1.6%, respectively. Further, in vitro drug release study showed preliminary burst release in 2 h followed by a sustained release for 36 h in phosphate buffer at different pH (4.0, 5.5, and 7.4) as compared to free drug. Drug release was found to be pH dependent, as the pH was increased, the drug release rate was found to be low. Time-dependent cell viability assay exhibited significant higher cell viability and higher internalization than free AZA in MCF-7 cells. AZA-LIPO were more effective than the free AZA in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. The result showed that the formulated biocompatible AZA-LIPO nano-formulations may be used as an efficient anti-cancer drug delivery system for the treatment of breast cancer after establishing preclinical and clinical studies.

Ciprofloxacin (Cf) is antibiotic used oculary for treatment of conjunctivitis and corneal ulcers. The barriers for its use are: high dosage frequency and poor solubility lead to ocular irritation. This study sought to develop ciprofloxacin-cubosomal (Cf-Cub) in situ gel in order to improve eye permeation, prolong the ocular retention time, and enhance its antimicrobial activity. Box-Behnken design was used to prepare cubosomes. Three independent variables were; Phytantriol amount, Lutrol amount, and hydration media pH, while particle size, encapsulation, and steady state flux were evaluated as dependent variables. The optimised cubosomes were evaluated for antimicrobial activity, and in vivo estimation of Cf in the aqueous humour of rabbits’ eyes. The results indicated that, the optimised formula consisted of 60 mg of Cf, 100 mg phytantriol, 25 mg Lutrol, and hydration media pH equal 5.8 produced cubosomes with 121 nm size, 75% entrapment, and 2.54 times antimicrobial activity compared with commercially eye drops. The estimation of Cf in aqueous humour indicated that once daily administration of the optimised formula maintain the drug concentration above MIC compared with commercial drops which require four times daily administration. This confirmed that optimised formula improved eye permeation, prolonged the ocular retention time, and enhanced the antimicrobial activity.

The present investigation was undertaken to develop a statistically and optimized omega-3-phospholipid based nanotransfersomes [NTFs] loaded with Pravastatin sodium [PVS] and Naringin [NG] in order to reverse the PVS induced hepatic marker enzymes elevation, decrease lipid peroxidation, and enhance the anti-oxidant cascade. NTFs were developed by a modified thin-film hydration technique using omega-3- phospholipids and sodium deoxycholate. The composition of the NTFs was statistically optimized by the design of Experiments using Box–Behnken design with three factors at three levels. They were characterized for size, EE%, ex-vivo permeation, and in-vivo hepatic markers enzymes level estimation. Omega-3-phospholipid has the most prominent effect on the particle size, followed by sodium deoxycholate. However, EE [%] is mostly affected by sodium deoxycholate, followed by omega-3-phospholipid. The optimized NTFs showed particle size, EE%, and cumulative % permeation of 191 nm, 76% and 55% respectively. The in-vivo study of optimized formulation revealed that NG act synergistically with omega-3-phospholipids, and potentially reverse the hepatic marker enzymes [ALT], and lipid peroxidative markers [MDA] induced by PVS to 54 IU/L and 45 mmol/mg protein respectively.

Bader Mubarak Aljaeid,1 Khaled Mohamed Hosny1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt Background and objective: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (2.5-fold. Conclusion: MN-SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. Keywords: miconazole, Precirol ATO5, solid lipid nanoparticles, encapsulation, Cremophor RH40, antifungal activity

The aim of the present study was to develop and examine a new non-invasive injectable graft for the repair of alveolar bone clefts using recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated within injectable liposomal in situ gel (LIG).Different liposomal formulations loaded with rhBMP-2 were prepared, and the effects of the preparation methods and lipid content on the efficiency of rhBMP-2 encapsulation within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum (DGG) was used, and the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetics and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and treated with different injectable formulae, including rhBMP-2 liposomes and in situ gel (rhBMP-2-LIG).The results indicated that the prepared rhBMP-2-LIG prolonged the release and residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated using this novel formula.BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities.

MgO nanoparticles have been recently discovered as an antibacterial, however, they limited by property degradation due to agglomeration. The addition of a coating agent, such as a zein polymer, is effective in preventing agglomeration without affecting nanosized properties. The aim of this study was to assess the antimicrobial property of MgO nanoparticles when coated with a zein polymer against several oral bacteria and fungi. This was done by utilizing various assessment techniques. The ultimate aim is to use these nanoparticles in dental preparations. The antimicrobial activity of zein-coated MgO nanoparticles at different concentrations of 0.5, 1 and 2% were tested against four different microorganisms: Staphylococcus aureus, Streptococcus mutans and Enterococcus faecalis (gram positive bacteria), and Candida albicans (as oral fungus). Two different techniques were utilized: the Kirby-Bauer test, and a modified direct contact test. The results indicated that the antibacterial effect of 1% or 2% zein-coated MgO nanowires were statistically significant (p0.05) against the four organisms studied: S. mutans, S. aureus, E. faecalis and C. albicans. Zein-coated MgO nanoparticles are a new human friendly and potent antimicrobial agent that can be incorporated in the formulation of a variety of new dental materials and products that should provide improvements in dental care and oral health.

Solid lipid nanoparticles (SLNs) are prospective carriers for oral delivery of poorly soluble drugs with low bioavailability. Therefore, the study aimed at developing carvedilol (CVD) in SLNs to control its release and enhance its bioavailability in the management of hypertension, and cardiac diseases. Box-Behnken design (BBD) was applied to optimize the variables affecting the quality of CVD-SLNs which prepared by homogenization-ultrasonication technique. The concentrations of Percirol (X1), Gelucire (X2), and stearylamine (X3) were chosen as the crucial independent variables. The dependent variables were estimated and analyzed by Statgraphics software to achieve the optimum characteristics of the developed SLNs. The optimized SLNs was evaluated in vitro and in vivo for pharmacokinetic parameters on male New Zealand white rabbits. The results of this study revealed that the CVD-SLNs have a colloidal size of 31.3 nm with zeta potential of 24.25 mV indicating good stability and 91.43% entrapment efficiency. The in vitro release of CVD from the SLNs was best fitted to Hixon-Crowell model that describes the release from the particles with uniform size. The in vivo pharmacokinetics results indicated the prolongation in the mean residence time of CVD to 23 h when delivered in SLNs and its oral bioavailability enhanced by more than 2-folds.

Khaled Mohamed Hosny,1,2 Hisham Ahmed Mosli,3 Ali Habiballah Hassan4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 3Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department ofOrthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Sildenafil citrate (SC), a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays inadequate aqueous solubility, which delays the onset of its action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40%) bioavailability. Third, the gastrointestinal effects of SC include dyspepsia and a burning sensation. The aim of this research was to prepare SC as a sublingual tablet utilizing soy polysaccharide as novel superdisintegrant to mitigate the abovementioned problems. The solubility of SC in various hydrophilic carrier solutions was estimated in order to prepare the drug as a coprecipitate. Sublingual tablets were prepared and evaluated for hardness, friability, drug content, wetting time, water absorption ratio, in vitro dispersion time, dissolution rate, and stability study. The pharmacokinetic study of the tablets was carried out on healthy volunteers. The results indicated that the co-precipitation of SC with polyvinylpyrollidone K30 enhanced the solubility of SC by more than eight folds. The tablet contained 8% soy polysaccharide as a superdisintegrant and provided a wetting time of 25seconds, and in vitro dispersion times of 55seconds. The drug release was found to be 95.6%. The prepared SC sublingual tablet also exhibited a rapid onset of action, and its bioavailability was enhanced 1.68-fold compared with that of the marketed tablets. It can be concluded that SC sublingual tablet is a promising formulation that results in higher solubility, faster dispersion and onset of action, higher release rate, and higher systemic bioavailability. Keywords: bioavailability, erectile dysfunction, onset of action, polyvinylpyrrolidone, Emcosoy

Preparation of an optimized finasteride (FSD) lyophilized tablets loaded with self-nanoemulsifying drug delivery system (SNEDDS).Enhance FSD bioavailability in male pattern baldness and benign prostatic hyperplasia.Two-step optimization was implemented to achieve the study goals. First; the mixture design was used to develop an optimized SNEDDS through which the effect of cosurfactant number of carbon atoms on SNEDDS particle size and thermodynamic stability has been tested. Second; the different tablet excipients have been used to develop an optimized self-nanoemulsifying lyophilized tablets (SNELTs). The prepared tablets have been fully characterized. Interaction among tablet components has been studied. Finally, FSD clinical pharmacokinetic has been investigated on human volunteers.Anise oil and tween 80 were selected as oily phase and surfactant, respectively while different aliphatic alcohols were studied as cosurfactants. Percentages of oil, surfactant, and cosurfactants were significantly affecting SNEDDS particle size. Increasing cosurfactant number of carbon atoms achieved smaller particle size and higher stability. The optimized SNEDDS was found to contain 10.3455, 45.8972, and 43.7573% of anise oil, tween 80, and butanol, respectively. Variations in FSD cumulative release and disintegration time, from the prepared tablets, were attributed to change in the percent of plasdone XL, Avicel and silica. No interaction among components was noticed. Clinical pharmacokinetics illustrated significant enhancement in the studied parameters from the optimized lyophilized tablets loaded with drug SNEDDS when compared to marketed FSD product.Lyophilized tablets could be considered as a good alternative for conventional solid dosage forms especially when loaded with drug nanosystems.

Purpose: To formulate and evaluate an antispasmodic drug, mebeverine hydrochloride (Mbv-HCl), as a local anesthetic mucoadhesive buccal tablet. Methods: Mbv-HCl loaded tablets were formulated, using a direct compression technique, with varying polymer concentrations including carbopol 934P alone, carbopol 934P/hydroxypropyl methylcellulose (HPMC) mixture, or carbopol 934P/chitosan mixture. The tablets were evaluated for physicochemical characteristics, in-vitro drug release, bioadhesive strength, swelling, ex-vivo residence time, ex-vivo permeation, drug permeation through the buccal membrane of sheep, and stability. Results: The results indicate that formulation F4, which contains HPMC/carbopol 934P (3:1), showed the best in-vitro drug release profile. The release kinetics for all the formulations fitted well with Hixson- Crowell kinetic model. Bioadhesive strength, surface pH, and swelling index of F4 were 41.52, 6.36, and 231.2 %, respectively. Maximum residence time ex-vivo was exhibited by formulation F4, showing a maximum residence time of about 330 min with 80 % of Mbv-HCl permeated in 6 h ex-vivo . F4 was stable after storage for 60 days at 25 o C/60 % RH and 40 o C/75 % RH, with non-significant change ( p < 0.05) in drug content, bioadhesive strength and in vitro release. Conclusion: The optimized mucoadhesive buccal formulation is promising for delivery of Mbv-HCl, and displays high bioadhesion and adequate permeability through sheep buccal membrane to achieve a local anesthetic action. Keywords: Mebeverine hydrochloride, Buccal, Mucoadhesive tablet, Swelling index, Bioadhesive strength, Local anesthetic

Docosahexaenoic acid is a omega-3-fatty acid which together with other long-chain omega-3-fatty acid known to have protective effect against various diseases including hypertension, myocardial infarction, Alzheimer disease, and cancers. Poor bioavailability owning to limited aqueous solubility limits its effective therapeutic delivery. Self-nanoemulsifying drug delivery systems are known to enhance the systemic absorption of poorly bioavailable lipophilic bioactive/therapeutics compounds. The purpose of this work was to investigate the potential of self-nanoemulsifying drug delivery systems produced by spontaneous nanoemulsification to enhance the oral bioavailability of docosahexaenoic acid. Initially, the screening of oil, surfactant, and cosurfactant was carried out by determining the miscibility and emulsifiability of the component with docosahexaenoic acid. Docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems were prepared using Capryol 90, Tween 20, and polyethylene glycol 200 due to their excellent miscibility and emulsifiability with docosahexaenoic acid. Docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems’ droplet size, size distribution, and zeta potential were found to be 111.5 ± 4.2 nm, 0.269 ± 0.05 nm, and −23.53 ± 2.9 mV, respectively. The in vitro drug release and ex vivo absorption studies showed better in vitro release and intestinal absorption as compared to docosahexaenoic acid aqueous dispersion. In vivo studies demonstrated a significant increase ( p < 0.001) in the oral bioavailability of docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems in comparison to a docosahexaenoic acid aqueous dispersion. This indicated the potential of self-nanoemulsifying drug delivery systems as an effective unit dosage form for the oral delivery of docosahexaenoic acid.

Saquinavir mesylate (SM) is a protease inhibitor with activity against human immunodeficiency virus type 1 (HIV-1) and is available in tablet form, which has three major problems. First, the drug undergoes extensive first pass metabolism. Second, the drug has a poor aqueous solubility. And third, it has low GIT permeability and absorption. These constrains lead to decrease oral bioavailability (4% only) and administration of large doses which increase the incidence of occurrence of the side effects. The aim of this research was to utilize nanotechnology to formulate (SM) into a nasal in situ nanosized microemulsion gel (NEG) to provide a solution for the previously mentioned problems. The solubility of (SM) in various oils, surfactants, and cosurfactants was estimated. Pseudo-ternary phase diagrams were developed and various nanosized microemulsion (NE) were prepared, and subjected to characterization, stability study, and droplet size measurements. Gellan gum was used as an in situ gelling agent. The gel strength, critical ionic concentration, gelation characteristics, in vitro release, and ex vivo nasal permeation were determined. The pharmacokinetic study was carried out in rabbits. Stable NEs were successfully developed with a droplet size range of 25-61 nm. A NEG composed of 17.5% Labrafac PG, 33% Labrasol, and 11% Transcutol HP successfully provided the maximum in vitro and ex vivo permeation, and enhanced the bioavailability in the rabbits by 12-fold when compared with the marketed tablets. It can be concluded that the nasal NEG is a promising novel formula for (SM) that has higher nasal tissue permeability and enhanced systemic bioavailability.