Percutaneous Absorption of Salicylic Acid after Administration of Trolamine Salicylate Cream in Rats with Transcutol® and Eucalyptus Oil Pre-Treated Skin

Purpose: This study was conducted to assess the effect of skin pre-treatment with Transcutol® and eucalyptus oil on systemic absorption of topical trolamine salicylate in rat. Methods: Pharmacokinetic parameters of salicylic acid following administration of trolamine salicylate on rat skin pre-treated with either Transcutol® or eucalyptus oil were determined using both non-compartmental and non-linear mixed effect modeling approaches and compared with those of control group. Results: Median (% of interquartile range/median) of salicylic acid AUC0-8hr (ng/mL/hr) values in Transcutol® or eucalyptus oil treated rats were 2522(139%) and 58976(141%), respectively as compared to the 3023(327%) of the control group. Skin pre-treatment with eucalyptus oil could significantly decrease extravascular volume of distribution (V/F) and elimination rate constant (k) of salicylic acid. Conclusion: Unlike Transcutol®, eucalyptus oil lead to enhanced transdermal absorption of trolamine salicylate through rat skin

Nanomedicine for Immunosuppressive Therapy: Achievements in Pre-Clinical Research

Introduction: Immunosuppression is the mainstay therapy in organ transplantation and autoimmune diseases. The effective clinical application of immunosuppressive agents has suffered from the emergence of systemic immunosuppression and/or individual drug side effects. Nanotechnology approaches may be used to modify the mentioned shortcomings by enhancing the delivery of immunosuppressants to target cells of the immune system, thus reducing the required dose for function, and/or reducing drug distribution to non-target tissues. Areas covered: We provide an overview on the development of nanotechnology products for the most commonly used immunosuppressive agents. At first, the rationale for the use of nanoparticles as means for immunosuppressive therapy is discussed. This is followed by a review of major accomplishments in this area, particularly in preclinical in vivo studies. Expert opinion: The results of research conducted in this area to date, points to a great promise for nano-medicine in increasing the bioavailability, reducing the toxicity, and/or potentiating the activity of immunosuppressive agents. It is, therefore, safe to speculate the more rapid translation of nanotechnologyin clinical immunosuppressive therapy in the near future providing to the overcoming of hurdles associated with nano-drug delivery such as high cost, inadequate reproducibility and potential safety concerns of the delivery systems themselves

Indomethacin electrospun nanofibers for colonic drug delivery: in vitro dissolution studies

Generally, although the conventional drug delivery systems, such as using only pHdependent polymers or time-dependent release systems are popular, the individuals’ variations of physiological conditions usually lead to premature or imperfect drug release from each of these systems. Therefore, a combination of pH- and time-dependent polymers could be more reliable for delivering drugs to the lower GI tract such as colon. To this end, electrospinning method was used as a fabrication approach for preparing electrospun nanofibers of indomethacin aimed for colon delivery. Formulations were prepared based on a 3 2 full factorial design. Independent variables were the drug:polymer ratio (with the levels of 3:5, 4.5:5 and 6:5 w/w) and Eudragit S:Eudragit RS w/w ratio (20:80, 60:40 and 100:0). The evaluated responses were drug release at pH 1.2, 6.4, 6.8 and 7.4. Combinations of Eudragit S (ES), Eudragit RS (ERS) and drug based on factorial design were loaded in 10 ml syringes. 3 Electrospinning method was used to prepare electrospun nanofibers from electrospinning solutions. Conductivity and the viscosity of the solutions were analyzed prior to electrospinning. After collection, the nanofibers were evaluated in terms of morphology and drug release. It was shown that the ratio of drug:polymer and polymer:polymer were pivotal factors to control the drug release from nanofibers. A formulation containing Eudragit S:Eudragit RS (60:40) and drug:polymer ratio of 3:5 exhibited the most appropriate drug release as a colon delivery system with a minor release at pH 1.2, 6.4 and 6.8 and major release at pH 7.4. Nanofibers resulted from this formulation were also more uniform and contained fewer amounts of beads. It was demonstrated that the electrospinning could be regarded as a modern approach for the preparation of colon drug delivery systems leading to marketable products

Development and Evaluation of a Solid Self-Nanoemulsifying Drug Delivery System for Loratadin by Extrusion-Spheronization

Purpose: Recently the liquid nanoemulsifying drug delivery systems (SNEDDS) have shown dramatic effects on improving oral bioavailability of poorly soluble drugs. The main purpose of this study was to prepare a solid form of self-nanoemulsifying drug delivery system of loratadin by extrusion-spheronization. The liquid SNEDDS are generally prepared in a soft or hard gelatin capsules which suffers from several disadvantages. Therefore incorporation of SNEDDS into solid dosage form is desirable to get together the advantages of SNEDDS and solid multiparticualte systems. Methods: The SNEDDS was consisted of liquid paraffin, capriole, span 20, transcutol and loratadin as a poorly soluble drug. A multilevel factorial design was used to formulation of SNEDDS pellets, liquid SNEDDS (20 and 30%) was mixed with lactose, microcrystallin cellulose (40%) and silicon dioxide (0, 5 and 10%), and Na- crosscarmelose (0, 5 and 10%). The resulting wet mass transformed into pellets by extrusion-spheronization. The pellets were dried and characterized for size (sieve analysis), shape (image analysis), mechanical strength (friability test), droplet size (laser light scattering) and drug release rate (dissolution test). Selected SNEDDS pellets were also compared with conventional loratadin pellet or tablet formulation. Results: The resulting SNE pellets exhibited uniform size and shape. Total friability of pellets did not affected by formulation variables. The in vitro release of SNE pellets was higher than the liquid SNE and powder tablets. Conclusion: Our studies demonstrated that extrusion-spheronization is a viable technology to produce self-emulsifying pellets in large scale which can improve in vitro dissolution with better solubility

Effect of Anionic Polymers on Drug Loading and Release from Clindamycin Phosphate Solid Lipid Nanoparticles

Purpose: To develop and characterize solid lipid nanoparticle (SLN) systems containing dextran sulfate or sodium alginate as anionic polymers for the delivery of clindamycin phosphate as a model hydrophilic cationic drug. Methods: A multi-level factorial design was used for the preparation and optimization of clindamycin SLNs. Polymers (dextran sulfate and sodium alginate), Tween 80, and Pluronic F68 were chosen as the independent variables. The SLNs were prepared using stearic acid as the lipid matrix by an emulsion congealing technique with cold homogenization. Particle size and drug loading were evaluated as the primary responses. The morphology and drug release rate of the selected formulations were also determined. Results: The results revealed that incorporation of anionic polymers increased drug loading of the SLNs. Dextran sulfate had a greater effect on drug loading, increasing it from 1.32 to 18.19 %, compared to the 6.73 % achieved using sodium alginate. Dextran sulfate also reduced drug release rate by half compared with sodium alginate, probably due to the higher charge density, lower molecular weight and lower branching density of the ionic polymer. Conclusion: Incorporation of anionic polymers can increase the loading of clindamycin phosphate into SLNs. Drug release from SLNs is also dependent on the polymer type

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood