Fabrication of controlled-release polymeric microneedles containing progesterone-loaded self-microemulsions for transdermal delivery.

Progesterone (PG) has been approved for hormone replacement therapy to mitigate the risk of endometrial carcinoma. However, there has been a lack of success in oral PG due to its rapid degradation. Transdermal PG has advantages but lacks efficacy due to its poor solubility (Log p = 3.9). Therefore, this study aimed to evaluate how combining self-microemulsifying drug delivery systems (SMEDDS) and polymeric microneedles (MNs) could improve the transdermal delivery of PG in a controlled-release manner. Among PG-SMEDDS, PG-SME5 was selected for its desirable properties and stability. The two-layer polymeric MNs formulation incorporating PG-SME5 (PG-SMEDDS-tMNs) was formulated from aqueous blends of polymers as a first layer and 20% PCL as a second layer. It successfully penetrated neonatal porcine skin with the dissolution of the first layer observed within 15 min after application. In vitro skin permeation revealed that the percentage of PG which permeated the skin over 82 h using PG-SMEDDS-tMNs was higher than a PG-suspension and PG-SMEDDS. The Higuchi kinetic showed controlled release over 15 days of PG from PG-SMEDDS-tMNs. These studies suggested that incorporating PG-SMEDDS into controlled-release two-layer polymeric MNs could be a promising approach for improving the transdermal delivery of PG.

Rapid Microwave-Assisted Synthesis of pH-Sensitive Carbon-Based Nanoparticles for the Controlled Release of Doxorubicin to Cancer Cells.

Carbon-based nanoparticles (CNPs) are a new type of interesting nanomaterials applied in various pharmaceutical fields due to their outstanding biocompatible properties. Novel pH-sensitive CNPs were rapidly synthesized within 1 min by microwave-assisted technique for doxorubicin (DOX) delivery into five cancer cell lines, including breast cancer (BT-474 and MDA-MB-231 cell lines), colon cancer (HCT and HT29 cell lines), and cervical cancer (HeLa cell lines). CNPs and DOX-loaded CNPs (CNPs-DOX) had nano-size of 11.66 ± 2.32 nm and 43.24 ± 13.25 nm, respectively. DOX could be self-assembled with CNPs in phosphate buffer solution at pH 7.4 through electrostatic interaction, exhibiting high loading efficiency at 85.82%. The release of DOX from CNPs-DOX at pH 5.0, often observed in the tumor, was nearly two times greater than the release at physiological condition pH 7.4. Furthermore, the anticancer activity of CNPs-DOX was significantly enhanced compared to free DOX in five cancer cell lines. CNPs-DOX could induce cell death through apoptosis induction in MDA-MB-231 cells. The findings revealed that CNPs-DOX exhibited a promising pH-sensitive nano-system as a drug delivery carrier for cancer treatment.

Design and Optimization of 3D-Printed Gastroretentive Floating Devices by Central Composite Design.

This study aimed to optimize the size of capsule-shaped 3D-printed devices (CPD) using an experimental design by the response surface methodology to provide a gastroretentive drug delivery system (GRDDS) with optimal floating time. The CPD was fabricated using a fused deposition modeling (FDM) 3D printer. The central composite design was employed for the optimization of the devices. The morphology of the CPD was observed using a digital microscope and scanning electron microscope (SEM). The in vitro floating time and drug release were evaluated using a USP dissolution apparatus II. Appropriate total floating time (TFT) of the devices (more than 3 h) was obtained with the device's body, cap, and bottom thickness of 1.2, 1.8, and 2.9 mm, respectively. The release kinetics of the drug from the devices fitted well with zero-order kinetics. In conclusion, the optimization of CPD for GRDDS using the experimental design provided the devices with desirable floating time and ideal drug release characteristics.

Students' Perspectives and Achievements toward Online Teaching of Medicinal Chemistry Courses at Pharmacy School in Thailand During the COVID-19 Pandemic.

This communication was to share the efforts made in developing the fully online courses in medicinal chemistry during the educational disruption due to the coronavirus disease 2019 (COVID-19) pandemic. In the academic year 2020, the online course was implemented for the first time at the Faculty of Pharmacy, Silpakorn University, Thailand. Various online teaching strategies were integrated, raising the question of whether the developed online courses would deliver similar learning outcomes to the traditional classroom. At the end of each semester, the teaching assessment report was conducted and evaluated in 4 parts: part 1, evaluation of lecturer; part 2, student's self-evaluation; part 3, learning outcome development after studying the course; part 4, appropriateness of class environment and equipment. Overall, student responses toward parts 1-3 in the online class were as satisfactory as those in the previous on-site class. Lower scores toward part 4 were observed in the online class. In addition, student performance in terms of grade distributions between the on-site and online classes was different. On-site students earned the highest proportion of A grades, whereas online students earned a higher proportion of B+'s to F's. While the pandemic persists and the need for online courses remains, we hope that this communication will provide some educational insight and strategies to help in the ongoing efforts to adapt and establish more successful online courses.

Enabling Combinatorial siRNA Delivery against Apoptosis-Related Proteins with Linoleic Acid and α-Linoleic Acid Substituted Low Molecular Weight Polyethylenimines.

PURPOSE: Short interfering RNA (siRNA) therapy promises a new era in treatment of breast cancers but effective delivery systems are needed for clinical use. Since silencing complementary targets may offer improved efficacy, this study was undertaken to identify non-viral carriers for combinatorial siRNA delivery for more effective therapy. METHODS: A library of lipid-substituted polymers from low molecular weight polyethyleneimine (PEI), linoleic acid (LA) and α-linoleic acid (αLA) with amide or thioester linkages was prepared and investigated for delivering Mcl-1, survivin and STAT5A siRNAs in breast cancer cells. RESULTS: The effective polymers formed 80-190 nm particles with similar zeta-potentials, but the serum stability was greater for complexes formed with amide-linked lipid conjugates. The LA and αLA substitutions, with the low molecular weight PEI (1.2 kDa and 2.0 kDa) were able to deliver siRNA effectively to cells and retarded the growth of breast cancer cells. The amide-linked lipid substituents showed higher cellular delivery of siRNA as compared to thioester linkages. Upon combinational delivery of siRNAs, growth of MCF-7 cells was inhibited to a greater extent with 2.0PEI-LA9 mediated delivery of Mcl-1 combined survivin siRNAs as compared to individual siRNAs. The qRT-PCR analysis confirmed the decrease in mRNA levels of target genes with specific siRNAs and 2.0PEI-LA9 was the most effective polymer for delivering siRNAs (either single or in combination). CONCLUSIONS: This study yielded effective siRNA carriers for combinational delivery of siRNAs. Careful choice of siRNA combinations will be critical since targeting individual genes might alter the expression of other critical mediators.

Catechol-Functionalized Alginate Nanoparticles as Mucoadhesive Carriers for Intravesical Chemotherapy.

This research aimed to synthesize and evaluate mucoadhesive catechol-functionalized alginate (Cat-Alg) nanoparticles (NPs) for bladder cancer. Cat-Alg was synthesized using coupling chemistry, and the structure was verified using NMR and FT-IR. Cat-Alg NPs were generated by ionic gelation between the synthesized Cat-Alg and calcium chloride. Garcinia mangostana L. extract (GM extract) was entrapped into the NPs during particle formation. The physical characteristics, mucoadhesive properties, drug loading and release, cellular uptake, and anticancer activity of the GM extract-loaded NPs were investigated. The Cat-Alg NPs were spherical with sizes in the range of 155-186 nm. The slightly negative surface charge of the NPs provided them with excellent stability. The Cat-Alg NPs could be retained on a porcine bladder mucosa to a greater extent compared with unmodified Alg NPs. High loading efficiency (71.6%) and loading capacity (292 µg/mg) of GM extract in the NPs were achieved, and a constant release of GM extract was obtained for up to 8 h with zero-order kinetics. Moreover, the GM extract-loaded NPs were deposited in bladder tissue and accumulated in MB49 cells at a higher rate compared with GM extract suspension. In addition, the NPs could kill a mouse urothelial carcinoma cell line with low IC50. Therefore, these NPs have the potential to be a mucoadhesive drug delivery system for bladder cancer treatment. However, additional in vivo investigations are needed for clinical application in cancer treatment. Graphical abstract.

Influence of nanofiber alignment on the release of a water-soluble drug from cellulose acetate nanofibers.

Cellulose acetate nanofibers with different degrees of alignment (randomly aligned (RA), partially aligned (PA), and highly aligned (HA)) were produced using an electrospinning technique. The different degrees of alignment were obtained by adjusting the rotation speed of the collector. Alpha-arbutin (3% w/w) employed as a model water-soluble compound was incorporated into the nanofibers during the fabrication process. The drug release characteristics were investigated using the nanofiber mats with the same size and weight. The prepared nanofibers with different degrees of alignment showed similar physical characteristics, including the fiber diameter, drug loading efficiency and capacity, and molecular form of the drug in the fibers. Interestingly, alpha-arbutin was released from HA nanofibers at a significantly faster rate than the PA and RA nanofibers. Eighty percent of the drug was released into the medium in 1.7, 4.2, and 9.4 min for HA, PA, and RA nanofibers, respectively. The orientation of nanofibers played a crucial role in governing the drug release, probably by creating network meshes with different degrees of entanglement, affecting the diffusion of drug to the external medium. Consequently, this approach can be used as a simple means of achieving immediate-release or fast-acting characteristics of cellulose-based formulations containing a water-soluble drug.

HPMC/PVP Dissolving Microneedles: a Promising Delivery Platform to Promote Trans-Epidermal Delivery of Alpha-Arbutin for Skin Lightening.

Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 µg/cm2/h and 74.24 µg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 µg and 312.23 µg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.

Development of Chitosan-Based pH-Sensitive Polymeric Micelles Containing Curcumin for Colon-Targeted Drug Delivery.

pH-sensitive N-naphthyl-N,O-succinyl chitosan (NSCS) and N-octyl-N,O-succinyl chitosan (OSCS) polymeric micelles carriers have been developed to incorporate curcumin (CUR) for colon-targeted drug delivery. The physical entrapment methods (dialysis, co-solvent evaporation, dropping, and O/W emulsion) were applied. The CUR-loaded micelles prepared by the dialysis method presented the highest loading capacity. Increasing initial amount of CUR from 5 to 40 wt% to polymer resulted in the increase in loading capacity of the polymeric micelles. Among the hydrophobic cores, there were no significant differences in the loading capacity of CUR-loaded micelles. The particle sizes of all CUR-loaded micelles were in the range of 120-338 nm. The morphology of the micelles changed after being contacted with medium with different pH values, confirming the pH-responsive properties of the micelles. The release characteristics of curcumin from all CUR-loaded micelles were pH-dependent. The percent cumulative release of curcumin from all CUR-loaded micelles in simulated gastric fluid (SGF) was limited to about 20%. However, the release amount was significantly increased after contacted with simulated intestinal fluid (SIF) (50-55%) and simulated colonic fluid (SCF) (60-70%). The released amount in SIF and SCF was significantly greater than the release of CUR from CUR powder. CUR-loaded NSCS exhibited the highest anti-cancer activity against HT-29 colorectal cancer cells. The stability studies indicated that all CUR-loaded micelles were stable for at least 90 days. Therefore, the colon targeted, pH-sensitive NSCS micelles may have potential to be a prospective candidate for curcumin delivery to the colon.

Development of Microemulsions and Microemulgels for Enhancing Transdermal Delivery of Kaempferia parviflora Extract.

The purpose of this research was to develop microemulsions (ME) and microemulgels (MG) for enhancing transdermal delivery of Kaempferia parviflora (KP) extract. The methoxyflavones were used as markers. Various formulations of ME and MG containing 10% w/v KP extract were prepared, and the in vitro skin permeation and deposition were investigated. The potential ME system containing oleic acid (5% w/v), Tween 20 (20% w/v), PG (40% w/v), and water (35% w/v) was successfully formulated. ME with 10% w/v limonene (ME-L10%) showed higher methoxyflavones flux than ME-L5%, ME-L1%, ME without limonene, and KP extract in water, respectively. ME-L10% was selected for adding a gelling agent to form microemulgels (MG-L10%). However, the high viscosity of the gel formulation might control the diffusion of the compound from gel layer into the skin. Therefore, the liquid formulation provided potential ME droplets to deliver KP extract through the skin. Limonene also plays an effective role on the skin permeation, in which the histological image of the skin treated with ME-L10% exhibited larger space of each flattened keratinocyte layer in the stratum corneum compared to the skin treated with KP extract in water. Moreover, ME-L10% showed good stability. Therefore, ME-L10% was a potential formulation for improving transdermal delivery of KP extract.

Cationic Niosomes for Enhanced Skin Immunization of Plasmid DNA-Encoding Ovalbumin via Hollow Microneedles.

The purpose of the present study was to evaluate the use of cationic niosomes composed of Span20:cholesterol:cationic lipid (N 1,N 1-dimyristeroyloxyethyl-spermine) at the molar ratio of 2.5:2.5:0.5 mM combined with hollow microneedle (MN) devices for in vivo skin immunization of plasmid DNA-encoding ovalbumin (pOVA). The results revealed that using hollow MNs with cationic niosomes for pOVA penetration successfully induced both humoral and cell-mediated immune responses including immunoglobulin G (IgG) antibody responses, interleukin-4 (IL-4), and interferon gamma (IFN-γ) cytokine secretion. When using hollow MNs with cationic niosome/pOVA complexes, the immune response was superior to naked pOVA, which testifies the increased amount of IgG antibody responses and cytokine secretion. In comparison with conventional subcutaneous (SC) injections, using hollow MNs with cationic niosome/pOVA complexes induced a higher level of both IgG immune response and cytokine release. Moreover, a group of mice immunized with hollow MNs did not show infection or bleeding on the skin. Consequently, targeted delivery of pOVA using cationic niosomes combined with hollow MNs might prove a promising vaccination method for skin vaccination.

Influence of sonophoresis on transdermal drug delivery of hydrophilic compound-loaded lipid nanocarriers.

The effect of sonophoresis on the transdermal drug delivery of sodium fluorescein (NaFI)-loaded lipid nanocarriers such as liposomes (LI), niosomes (NI) and solid lipid nanoparticles (SLN) was investigated by confocal laser scanning microscopy (CLSM), fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The results showed that SN decreased the skin penetration of NaFI-loaded SLN (6.32-fold) and NI (1.79-fold), while it increased the penetration of NaFI-loaded LI (5.36-fold). CLSM images showed the red fluorescence of the LI and NI bilayer on the superficial layer of the stratum corneum. However, the red fluorescent probe of the SLN was not visualized in the skin. FTIR results of the LI and NI with SN showed no effect on lipid stratum corneum ordering, suggesting that the fragment of bilayer vesicles might repair the damaged skin. For SLN, the strengthening of stratum corneum by covering the disrupted skin with solid lipids was shown. SEM images show disrupted carriers of all the formulations adsorbed onto the damaged skin. In conclusion, the SN changed the properties of both the skin surface and lipid nanocarrier, demonstrating that disrupted skin might be repaired by a disrupted nanocarrier.

Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have been developed as an alternative for oral candidiasis treatment. NSCS was synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated into the micelles using various methods, including the dropping method, the dialysis method, and the O/W emulsion method. The size and morphology of the CZ-loaded micelles were characterized using dynamic light scattering measurements (DLS) and a transmission electron microscope (TEM), respectively. The drug entrapment efficiency, loading capacity, release characteristics, and antifungal activity against Candida albicans were also evaluated. The CZ-loaded micelles prepared using different methods differed in the size of micelles. The micelles ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The CZ released from the CZ-loaded micelles at much faster rate compared to CZ powder. The CZ-loaded NSCS micelles can significantly hinder the growth of Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal activity and might be further developed to be a promising candidate for oral candidiasis treatment.

Cationic niosomes an effective gene carrier composed of novel spermine-derivative cationic lipids: effect of central core structures.

CONTEXT: Cationic niosomes formulated from Span 20, cholesterol (Chol) and novel spermine-based cationic lipids of multiple central core structures (di(oxyethyl)amino, di(oxyethyl)amino carboxy, 3-amino-1,2-dioxypropyl and 2-amino-1,3-dioxypropyl) were successfully prepared for improving transfection efficiency in vitro. The niosomes composed of spermine cationic lipid with central core structure of di(oxyethyl)amino revealed the highest gene transfection efficiency. OBJECTIVES: To investigate the factors affecting gene transfection and cell viability including differences in the central core structures of cationic lipids, the composition of vesicles, molar ratio of cationic lipids in formulations and the weight ratio of niosomes to DNA. METHODS: Cationic niosomes composed of nonionic surfactants (Span20), cholesterol and spermine-based cationic lipids of multiple central core structures were formulated. Gene transfection and cell viability were evaluated on a human cervical carcinoma cell line (HeLa cells) using pDNA encoding green fluorescent protein (pEGFP-C2). The morphology, size and charge were also characterized. RESULTS AND DISCUSSION: High transfection efficiency was obtained from cationic niosomes composed of Span20:Chol:cationic lipid at the molar ratio of 2.5:2.5:0.5 mM. Cationic lipids with di(oxyethyl)amino as a central core structure exhibited highest transfection efficiency. In addition, there was also no serum effect on transfection efficiency. CONCLUSIONS: These novel cationic niosomes may constitute a good alternative carrier for gene transfection.

Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen via Microneedles.

The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8 h after administering with various conditions could be ranked as follows: hollow MN; high dose > medium dose > low dose > MN patch; high dose > medium dose > low dose > untreated skin; high dose > medium dose > low dose > without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500 µg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.

Skin Transport of Hydrophilic Compound-Loaded PEGylated Lipid Nanocarriers: Comparative Study of Liposomes, Niosomes, and Solid Lipid Nanoparticles.

The effect of surface grafting with N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG2000-DSPE) onto three types of lipid nanocarriers, liposomes, niosomes and solid lipid nanoparticles (SLNs) on the skin penetration of sodium fluorescein (NaFI) was investigated. Confocal laser scanning microscopy (CLSM) was used to visualize the penetration pathways. Fourier transform infrared spectroscopy (FT-IR) was used to determine the skin hydration. The results showed that the physicochemical properties of each nanocarrier were modified after PEG grafting. In the skin penetration study, PEG grafting increased the flux of NaFI-loaded PEGylated liposomes and significantly decreased the flux of NaFI-loaded PEGylated niosomes and NaFI-loaded PEGylated SLNs. The skin deposition study and CLSM images showed that the intact liposome vesicles permeated into the skin. The niosomes and SLNs had little or no vesicles in the skin, suggesting that NaFI may have been released from these nanocarriers before permeation. Additionally, the fluorescent CLSM images of the SLNs showed that NaFI deposited along the length of hair follicles inside the skin, indicating that the skin penetration route may be through the transfollicular pathway. For the PEGylated nanocarriers, the PEGylated liposomes had higher fluorescence intensities than the non-PEGylated liposomes, indicating higher NaFI concentrations. The PEGylated niosomes and PEGylated SLNs had lower fluorescence intensities than those of the non-PEG modified niosomes and SLNs. For FT-IR results, PEGylated liposomes increased the skin hydration, while the grafting PEG onto niosomes and SLN surfaces decreased the skin hydration. This study showed that the surface grafting of PEG onto various nanocarriers affected the skin transport of NaFI.

Development, Characterization and Skin Interaction of Capsaicin-Loaded Microemulsion-Based Nonionic Surfactant.

The aim of this study was to develop novel microemulsions (MEs) for the transdermal delivery of capsaicin. Microemulsion-based nonionic surfactants consisting of isopropyl myristate as the oil phase, various nonionic surfactants as the surfactant (S), various glycols or alcohol as the co-surfactant (CoS), and reverse osmosis water as the aqueous phase were formulated. Based on the optimal ME obtained from Design Expert, MEs containing a fixed concentration of oil, water or surfactant were prepared while varying the amounts of the other two fractions. The results indicated that the skin permeation flux of low dose capsaicin (0.15% (w/w)) was significantly higher for the selected ME than the commercial product and capsaicin in ethanol (control) by approximately two- and four-fold, respectively. We successfully demonstrated the feasibility of the transdermal delivery of capsaicin-loaded ME using a low concentration of nonionic surfactant and ethanol. Moreover, the optimization using computer program helped to simplify the development of a pharmaceutical product.

Application of Design Expert for the investigation of capsaicin-loaded microemulsions for transdermal delivery.

Our previous study reported that the Design Expert® Software showed a beneficial role in the development of microemulsions (ME) for transdermal drug delivery. To fully confirm the reproducibility and the reliability of simultaneous optimal ME formulations, the optimal ME formulations predicted by the Design Expert® Software were experimentally formulated and verified for their skin permeability. Ternary phase diagrams were used to predict the optimal ME area, and the ME formulations selected from outside this area were considered as candidate ME systems. Our ME systems were formulated with isopropyl myristate (IPM) as the oil phase, cocamide diethanolamine (DEA) as the surfactant, ethanol as a co-surfactant and water as the aqueous phase. The droplet size, size distribution, electrical conductivity, pH, drug content and skin permeability of the candidate ME systems were monitored. Our findings indicated that the skin permeability of the optimal ME and all of the candidate ME formulations was significantly greater than that of the commercial capsaicin (CAP) product. Our study succeeded in predicting and developing the ME systems for the transdermal delivery of CAP. The simplex lattice design used in this study is experimentally useful for the development of pharmaceutical formulations.

Fabrication and Evaluation of Nanostructured Herbal Oil/Hydroxypropyl-ß-Cyclodextrin/Polyvinylpyrrolidone Mats for Denture Stomatitis Prevention and Treatment.

This work aims to develop the herbal oil-incorporated nanostructure mats with antifungal activity for the prevention and treatment of Candida-associated denture stomatitis. The nanofiber mats loaded with betel oil or clove oil were fabricated via electrospinning process. The morphologies and physicochemical properties of the herbal oil loaded nanofiber mats were examined using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and mechanical testing. The release characteristic, antifungal activity, and cytotoxicity were also investigated. The SEM images confirmed the homogeneous and smooth nanoscale fibers. The addition of the herbal oil into the nanofiber mats reduced the fiber diameters. The DSC and FT-IR results confirmed the presence of the oil in the nanofiber mats. The herbal oils can be released from the mats in a very fast manner and inhibit the growth of candida cells within only few minutes after contact. These nanofiber mats may be beneficial for the prevention and treatment of denture stomatitis.

Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins.

CONTEXT: The bitter taste of drug is masked by the exchange of ionized drugs with counter ions of ion exchange resin, forming "resinate". Cyclodextrin reduces the unpleasant taste and enhances the drug solubility by encapsulating drug molecules into its central cavity. OBJECTIVE: Oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin was developed, to mask the bitter taste and enhance drug dissolution. METHODS: Meloxicam (MX) was selected as a model drug. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-ß-cyclodextrin (HPßCD) or MX/HPßCD complexes, and a mixture of resinate and MX/HPßCD complexes) were made by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste and stability. RESULTS AND DISCUSSION: The tablet hardness was ∼3 kg/in(2), and the friability was <1%. Tablets formulated with resinate and the mixture of resinate and MX/HPßCD complexes disintegrated rapidly within 60 s, which is the acceptable limit for ODTs. These results were corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HPßCD complexes provided complete MX dissolution and successfully masked the bitter taste. In addition, this tablet was stable at least 6 months. CONCLUSIONS: The combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste and enhance the dissolution of drugs that are weakly soluble in water.