Current Drug Delivery - Volume 16, Issue 10, 2019

Floating drug delivery system (FDDS) is the main approach to prolonging the gastric residence time in the stomach in which the bilayer floating tablet has the main role. It is more suitable for the treatment of local infections such as peptic ulcer, gastritis, Zollinger-Ellision syndrome, indigestion, and other local infections related to the gastrointestinal tract and also used for systemic applications. FDDS provides protection for those drugs which are acid labile and have a short half-life. It also improves bioavailability, reduces drug waste, and enhances the residence time of drugs. Nowadays, various technologies are being used for the development of FDDS. Novel drug delivery systems incorporation into bilayer floating tablets have also broadened the role of FDDS. Polymers have the main role in the development of FDDS, which serve as carriers for the drug and determine the gastric retention time and drug protection. FDDS is also an easy, cheap, and more convenient method for dual drug delivery of drugs.

Blood-brain barrier (BBB) provides restrictions for the transportation of various therapeutic agents to the brain. Efforts to directly target the brain by olfactory as well as trigeminal nerve pathway, bypassing BBB, have grown significantly in recent times. The intranasal route of transportation of the drug encompasses ability for the delivery of drug directly to the brain, improves site-specificity in the brain and avoids systemic side effects. In the current era, novel drug delivery systems are useful tools for targeting the brain without providing any harmful effects in nasal mucosa as well as the central nervous system. The complex structure of nasal cavity, mucociliary clearance, degradation by the enzymes present in nasal cavity and pathological conditions like rhinitis, common cold, etc. are the major disputes for nasal drug delivery. The use of nanotechnological approaches like solid lipid nanoparticles, polymeric nanoparticles, nanoemulsions, liposomes and polymeric micelles provides the ability to overcome these barriers. There are several emerging nasal drug delivery technologies produced by various pharmaceutical companies to conquer these hurdles. This review tries to address the recent developments in the area of direct drug delivery to the brain through the nasal route.

Background: Alzheimer’s disease is a chronic progressive neurodegenerative disorder associated with depletion of acetylcholine. Oral treatment with tacrine hydrochloride; a reversible inhibitor of acetylcholinesterase, finds limited use in Alzheimer’s disease due to frequent dosing, hepatotoxicity and extensive pre-systemic metabolism. Objectives: The objective of the study was to evaluate pharmacokinetic, pharmacodynamic, safety and stability profile of transdermal w/o nanoemulsion gel of tacrine hydrochloride and determine its relative bioavailability from transdermal nanogel in contrast to marketed capsule and conventional hydrogel. Methods: The optimized nanoemulsion gel NEGT4 (droplet size 156.4 ±0.48 nm, with poly dispersity index 0.36 ±0.4, permeation flux 6.172±2.94 μg/cm2/h across rat skin) was prepared by spontaneous emulsification followed by sonication. NEGT4 contained 7 mg of drug in 10% w/w distilled water, 30% w/w surfactant (Labrafil M) and cosurfactant (Transcutol P) mixture in ratio 1:4 and 60 % Capryol 90 as oily phase thickened with 98.9 mg ethyl cellulose (20 cps). In vivo studies were carried out on male Wistar rats following standard guidelines. Scopolamine was used to induce amnesia in rats which is a characteristic of Alzheimer’s disease. Various formulations were compared by performing pharmacokinetic, histopathological, behavioural and biochemical studies on rats. Stability studies on nanoemulsion gels were carried out in accordance with The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. Results: Pharmacokinetic studies exhibited significantly greater extent of absorption from NEGT4 in comparison to capsule and hydrogel with a 2.18 and 5.26-fold increase respectively. Significant improvement in neurobehavioral parameters was observed with NEGT4 in scopolamine-induced amnesic rats. Biochemical assessment showed superior anti-amnesic activity of NEGT4 through augmentation of antioxidant enzymes, decreased lipid peroxidation and acetylcholinesterase activity. Low value of serum aminotransferase in rats treated with NEGT4 indicated the absence of hepatotoxicity. NEGT4 was found to be non-irritant and possessed a shelf life of 4.11 years. Conclusion: Developed nanoemulsion gel of tacrine hydrochloride was found to be safe, stable, and efficacious and has immense potential to be used in the therapy of Alzheimer’s disease.

Background: This paper presents the effect of solution properties and operating parameters of polyethylene oxide (PEO) based nanofiber using a wire electrode-based needleless electrospinning. Methods: The feed solution was prepared using a PEO dissolved in water or a water-ethanol mixture. The PEO solution is blended with Bovine Serum Albumin protein (BSA) as a model drug to study the effect of the electrospinning process on the stability of the loaded protein. The polymer solution properties such as viscosity, surface tension, and conductivity were controlled by adjusting the solvent and salt content. The morphology and fiber size distribution of the nanofiber was analyzed using scanning electron microscopy. Results: The results show that the issue of a beaded nanofiber can be eliminated either by increasing the solution viscosity or by the addition of salt and ethanol to the PEO-water system. The addition of salt and solvent produced a high frequency of smaller fiber diameter ranging from 100 to 150 nm. The encapsulation of BSA in PEO nanofiber was characterized by three different spectroscopy techniques (i.e. circular dichroism, Fourier transform infrared, and fluorescence) and the results showed the BSA is well encapsulated in the PEO matrix with no changes in the protein structure. Conclusion: This work may serve as a useful guide for a drug delivery industry to process a nanofiber at a large and continuous scale with a blend of drugs in nanofiber using a wire electrode electrospinning.

Background: It has been shown that curcumin (Cur) has anti-plasmodial activity; however, its weak bioavailability, rapid metabolism, and limited chemical stability have restricted its application in clinical usages. Nanostructured lipid carriers (NLCs) are a type of Drug-Delivery Systems (DDSs) whose core matrix is composed of both solid and liquid lipids. Objective: The aim of the current study was to prepare and characterize curcumin-loaded nanostructured lipid carriers (Cur-NLC) for malaria treatment. Methods: For producing NLC, coconut oil and cetyl palmitate were selected as a liquid and solid lipid, respectively. In order to prepare the Cur-NLC, the microemulsion method was applied. General toxicity assay on Artemia salina as well as hemocompatibility was investigated. Anti-plasmodial activity was studied on mice infected with Plasmodium berghei. Results: The NLCs mean particle size and Polydispersity Index (PI) were 145 nm and 0.3, respectively. Further, the zeta potential of the Cur-NLC was −25 mV. The NLCs indicated a pseudo-spherical shape observed via transmission electron microscopy (TEM). The loading capacity and encapsulation efficacy of the obtained Cur-NLC were 3.1 ± 0.015% and 74 ± 3.32%, respectively. In vitro, Cur release profiles showed a sustained-release pattern up to 5 days in the synthesized Cur-NLC. The results of in vivo antiplasmodial activity against P. berghei revealed that antimalarial activity of Cur-NLC was significantly higher compared with that of free Cur at the dose of 40 mg/kg/day. Conclusion: The results of this study suggested that NLC would be used as a potential nanocarrier for the treatment of malaria.

Background: The loop diuretic drug furosemide is widely used for the treatment of edema in various conditions, such as pulmonary, cardiac and hepatic edema, as well as cardiac infarction. Furosemide, due to its poor water solubility and low bioavailability after oral administration of conventional dosage form, is categorized as class IV in the biopharmaceutical classification system. Objective: In the case of furosemide, this release profile is responsible for various physiological problems, acute diuresis being the most serious. This adverse effect can be circumvented by the modified release of furosemide from tablet formulations compared to those forms designed for immediate release. Methods: In this report, a D-optimal combined experimental design was applied for the development of furosemide containing bilayer and compression coated tablets, aiming at lowering the drug’s burst release in the acidic environment of the stomach. A D-optimal combined design was selected in order to include all requirements in one design with many levels for the factors examined. The following responses were selected as the ones reflecting better criteria for the desired drug release: dissolution at 120 min (30-40%), 300 min (60-70%) and 480 min >95%. The new formulations, suggested by the Doptimal combined design, incorporated different grades of Eudragit ® polymers (Eudragit® E100 and Eudragit® L100-55), lactose monohydrate and HPMC K15M. The dissolution profile of furosemide from these systems was probed via in vitro dissolution experiments in buffer solutions simulating the pH of the gastrointestinal tract. Results: The results indicate that the use of Eudragit® E100 in conjunction with lactose monohydrate led to 21.32-40.85 % drug release, in the gastric medium, in both compression-coated and bilayer tablets. This is lower than the release of the mainstream drug Lasix® (t=120 min, 44.5% drug release), implying longer gastric retention and drug waste minimization. Conclusion: Furosemide’s release in the intestinal environment, from compression coated tablets incorporating Eudragit® L100-55 and HPMC K15M in the inner core or one of the two layers of the bilayer tablets, was delayed, compared to Lasix®.

Background: In this study, a liposomal gel based on a pH-gradient method was used to increase the skin-layer retention of monocrotaline (MCT) for topical administration. Methods: Using the Box-Behnken design, different formulations were designed to form liposome suspensions with optimal encapsulation efficiency (EE%) and stability factor (KE). In order to keep MCT in liposomes and accumulate in skin slowly and selectively, MCT liposome suspensions were engineered into gels. Results: A pH-gradient method was used to prepare liposome suspensions. The optimal formulation of liposome suspensions (encapsulation efficiency: 83.10 ± 0.21%) was as follows: MCT 12 mg, soybean phosphatidyl choline (sbPC) 200 mg, cholesterol (CH) 41 mg, vitamin E (VE) 5 mg, and citric acid buffer solution (CBS) 4.0 10 mL (pH 7.0). The final formulation of liposomal gels consisted of 32 mL liposome suspensions, 4.76 mL deionized water, 0.40 g Carbopol-940, 1.6 g glycerol, 0.04 g methylparaben, and a suitable amount of triethanolamine for pH value adjustment. The results of in vitro drug release showed that MCT in liposomal gels could be released in 12 h constantly in physiological saline as a Ritger-Peppas model. Compared with plain MCT in gel form, liposomal MCT in gel had higher skin retention in vitro. Conclusion: In this study, liposomal gels were formed for greater skin retention of MCT. It is potentially beneficial for reducing toxicities of MCT by topical administration with liposomal gel.

Objective: In this work, the loading of nicotine onto mesoporous silicate materials and its release into a phosphate buffer solution at 37°C were investigated. Methods: The mesoporous silicate materials designated as MCM-41 were prepared with different pore sizes via using alkyltrimethylammonium bromide surfactants with different alkyl chain lengths of carbon atoms 12, 14, and 16. The mesoporous silicate systems were characterized by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), N2-adsorption–desorption isotherms, and FT-IR spectroscopy. Results: Loading of nicotine was confirmed by FTIR and thermal gravimetric analysis and was determined by High-Performance Liquid Chromatography (HPLC). Conclusion: A slight increase in loading capacity with increasing pore size was observed, with a loading capacity of about 17% for MCM-41(16). The release of nicotine was monitored by HPLC and was almost complete for MCM-41(14) and MCM-41(16) in 8 h.