Iontophoresis: Skin Permeation Enhancement and Applications

Transdermal drug delivery (TDD) systems offer a number of potentialadvantages over conventional methods such as injectable and oraldelivery as they avoid the first pass metabolism and increase thepatient’s compliance. However, a major limitation of TDDs is that theskin is highly impermeable to macromolecules and hydrophilic drugs.The main barrier of drugs across the skin is the skin outermost layer,the stratum corneum. Application of electricity via the skin is one ofthe methods extensively used for enhancing drugs or chemicalsubstances through the skin. In this article, iontophoresis, a methodfor enhancing the skin permeation of hydrophilic drugs, macromolecules,and charged substances is reviewed. The article alsoelaborates on mechanisms that iontophoresis enhances skinabsorption which include electromigration, electroosmosis andpassive permeability. Factors affecting TDD systems usingiontophoresis including electric current, physicochemical properties ofdrug and physical properties of the skin are also discussed.Keywords:iontophoresis, skin permeation enhancement, factorsaffecting skin permeatio

Characterization and In Vitro Skin Permeation of Meloxicam-Loaded Liposomes versus Transfersomes

The goal of this study was to develop and evaluate the potential use of liposome and transfersome vesicles in the transdermal drug delivery of meloxicam (MX). MX-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (%EE), loading efficiency, stability, and in vitro skin permeation. The vesicles were spherical in structure, 90 to 140 nm in size, and negatively charged (−23 to −43 mV). The %EE of MX in the vesicles ranged from 40 to 70%. Transfersomes provided a significantly higher skin permeation of MX compared to liposomes. Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) analysis indicated that the application of transfersomes significantly disrupted the stratum corneum lipid. Our research suggests that MX-loaded transfersomes can be potentially used as a transdermal drug delivery system

Effect of particle size and diluent type on critical parameters for disintegration of tablets containing croscarmellose sodium as a disintegrant

Purpose: The aim of the present work was to determine the effect of particle size and type of diluents on critical concentration for the disintegration of tablet formulations containing a physical binary mixture of a superdisintegrant (croscarmellose sodium, CS) and a diluent.Methods: The diluents used in this study were microcrystalline cellulose (MCC), dibasic calcium phosphate (DCP) and pregelatinized starch (PGS). Each diluent was divided into 2 different size ranges (small and large size)) and further mixed with 0 - 100 % CS. The binary mixture was compressed at controlled pressure, and the disintegration time and physical characteristic of the tablets were evaluated.Results: The point of CS concentration that markedly affected the disintegration time of the tablets was recorded as the critical concentration for disintegration. The results showed that the particle size of the diluent did not affect the disintegration time. The critical CS concentrations were 2 % for DCP and MCC tablets and 5 % for PGS tablet. Adding a small amount of CS improved the disintegration of the tablets. However, increasing the amount of CS in the formulation also affected the hardness of the tablets. The particle size of diluents had a significant effect on the critical concentration for tablet disintegration.Conclusion: Determining the type and appropriate amounts of diluent and disintegrant (percolating component) may be useful in the design of tablet formulations.Keywords: Disintegration, Percolation threshold, Croscarmellose sodium, Microcrystalline cellulose, Dibasic calcium phosphate, Pre-gelatinized starc

Preparation and assessment of poly(methacrylic acid-coethylene glycol dimethacrylate) as a novel disintegrant

Purpose: To prepare and evaluate poly(methacrylic acid (MAA)-co-ethylene glycol dimethacrylate (EGD)) as a tablet disintegrant.Methods: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms at cross-linker (EGD) levels of 0.25 -16 % were synthesized and subjected to Fourier transform infrared spectroscopy. Swelling capacity, disintegration efficiency and cytotoxicity to Caco-2 cells were determined using standard procedures.Results: Poly(MAA-co-EGD) in acid (H) and sodium (Na) forms were successfully prepared. In contact with water, the polymers in Na form swelled more than those in H form. The swelling capacities of polymers in H and Na forms decreased with increasing amounts of cross-linker. Incorporation of the polymers accelerated the disintegration of microcrystalline cellulose tablets (placebo), and the disintegration efficiency depended on the salt form and amount of cross-linker. The Na salt form of the polymer crosslinked at 16 % EGD was the best candidate disintegrant. When used at 2.5 and 10 %, the selected polymer effectively promoted the disintegration and drug release of propranolol hydrochloride tablets. Moreover, cytotoxicity tests showed that it was non-toxic to Caco-2 cells.Conclusion: The developed poly(MAA-co-EGD) possesses good disintegration and dissolution functionalities. Thus, it may be adopted as a new super-disintegrant for fast-release tablets.Keywords: Tablet disintegrant, Methacrylic acid, Ethylene glycol dimethacrylate, Propranolol hydrochlorid

Preparation and characterization of N-benzyl-N,O-succinyl chitosan polymeric micelles for solubilization of poorly soluble non-steroidal anti-inflammatory drugs

Purpose: To investigate the solubilization of poorly water-soluble non-steroidal  anti-inflammatory drugs (NSAIDs) in N-benzyl-N,O-succinyl chitosan (BSCS)  polymeric micellesMethods: BSCS was synthesized by reductive amination and succinylation,  respectively. NSAIDs; meloxicam (MX), piroxicam (PRX), ketoprofen (KP) and indomethacin (IND) were entrapped in the hydrophobic inner cores by evaporation method. The effects of drug structure on loading efficiency, particle size and surface charge of micelles were investigated.Results: The critical micelle concentration of BSCS micelles was 0.0385 mg/mL and cytotoxicity on Caco-2 cells depends on the polymer concentration (IC50 = 3.23 ± 0.08 mg/mL). BSCS micelles were able to entrap MX, PRX, KP and IND and also improve the solubility of drugs. Drug loading efficiency was highly dependent on the drug molecules. The drug loading capacity of these BSCS micelles was in the following rank order: KP (282.9 μg/mg) > PRX (200.8 μg/mg) > MX (73.7 μg/mg) > IND (41.2 μg/mg). The highest loading efficiency was observed in KP-loaded BSCS micelles due to the attractive force between phenyl groups of KP and benzyl groups of the polymer. Particle size and surface charge were in the range of 312 - 433 nm and -38 to -41 mV, respectively.Conclusion: BSCS copolymer presents desirable attributes for enhancing the  solubility of hydrophobic drugs. Moreover, BSCS polymeric micelles might be beneficial carrier in a drug delivery system.Keywords: BSCS, polymeric micelles, solubilization, non-steroidal anti-inflammatory drug

การประยุกต์นาโนสตรักเจอร์ลิปิดแครีเออร์ในการนำส่งยา Applications of Nanostructured Lipid Carriers for Drug Delivery

Nanostructured lipid carriers (NLC) are second generation of lipidnanocarriers. NLC are colloidal carriers characterized by a solid lipid coreconsisting of a mixture of solid and liquid lipids and having a mean particlesize in the nanometer range. The NLC have many advantages (e.g.physical stability, protection of incorporated labile drugs from degradation,controlled relea se, excellent tolerability, easy to scale up and low cost ofexcipients). NLC formulations for various application routes (parenteral,oral, topical, ocular, pulmonary, and rectal) have been developed andthoroughly characterized in vitro and in vivo. NLC have been widely studiedas a next-generation delivery system in pharmaceuticals and cosmetics.The concept of surface modification is further increasing the importance ofNLC among the conventional colloidal carriers. In this article reviews aboutthe applications of NLC in the parenteral, oral, topical, ocular andpulmonary applications.Keywords: nanostructured lipid carriers, drug deliver

Synthesis of Polyethylene Glycol Diacrylate/Acrylic Acid Nanoparticles as Nanocarriers for the Controlled Delivery of Doxorubicin to Colorectal Cancer Cells

Doxorubicin (Dox) is known for its potential to deliver desirable anticancer effects against various types of cancer including colorectal cancer. However, the adverse effects are serious. This study aimed to synthesize polyethylene glycol diacrylate (PEGDA)/acrylic acid (AA)-based nanoparticles (PEGDA/AA NPs) for Dox delivery to colorectal cancer cells. The NPs were synthesized using free-radical polymerization reaction using the monomers PEGDA and AA with their physical properties, drug loading and release, biocompatibility, and anticancer effect evaluated. The NPs were spherical with a size of around 230 nm, with a 48% Dox loading efficiency and with loading capacity of 150 µg/mg. Intriguingly, the NPs had the ability to prolong the release of Dox in vitro over 24 h and were non-toxic to intestinal epithelial cells. Dox-loaded PEGDA/AA NPs (Dox-NPs) were able to effectively kill the colorectal cancer cell line (HT-29) with the Dox-NPs accumulating inside the cell and killing the cell through the apoptosis pathway. Overall, the synthesized PEGDA/AA NPs exhibit considerable potential as a drug delivery carrier for colon cancer-directed, staged-release therapy

Synthesis of N-vinylpyrrolidone/Acrylic acid nanoparticles for drug delivery: Method optimization

There are various approaches to deliver therapeutic agents to the preferred target. Polymeric nanoparticles were found to have pleasing suitability as a drug carrier. The goal of this research was to optimize the synthesis method to obtain the desirable %yield and particle properties of the new biocompatible polymer-based nanoparticles. The non-toxic polymer, N-vinyl pyrrolidone (NVP) and a widely used hydrophilic biocompatible acrylic acid (AA) monomer were used to form the drug nanocarriers. The synthesis method was optimized by changing the types of initiator (KPS or V50) and the monomers molar ratio (NVP:AA). It was found that by varying both the monomer molar ratio and the type of reaction initiator, did not have significant effect on the physicochemical characteristics of the nanocarriers. The FTIR spectra of all products exhibited the peaks of carboxylic acid, carbonyl, and tertiary amine functional group vibration. The particle size of the nanocarriers was in the range of 173.6 ± 18.4 to 201.4 ± 17.1 nm with negative surface charge. However, the yield obtained increased as the initiator was altered from KPS to V50, and when the acrylic acid molar ratio was increased from 1:1 to 1:3. In conclusion, changing the initiator and monomer molar ratio may affect the physicochemical properties of the nanocarriers and the %yield of the nanocarrier product. Further investigations are essential to obtain the favorable drug nanocarriers for drug delivery