Effect of Nutrient Formulations on Permeation of Proteins and Lipids through Porcine Intestine In vitro

Purpose: To investigate the effect of nutrient formulations on the permeation of proteins and lipids through porcine intestine in vitro.Method: In vitro permeation studies of proteins and lipids of two peptide-based formulations, composed of various compounds and sources of hydrolyzed protein was carried out, and compared with a conservative polymeric formulation as control, The test was undertaken using Franz diffusion cell apparatus incorporating porcine intestine.Results: The peptide-based formulation demonstrated higher protein absorption than the conservative polymeric one. However, there were some differences in protein absorption rates between the peptide based formulations obtained from various sources. Formulation A with 1.0 and 1.5 kcal/mL exhibited significantly (p < 0.05) higher cumulative protein permeation (11.97 ± 0.23 and 12.54 ± 0.94 μg/cm2) than formulations B (9.41 ± 0.36 and 9.67 ± 0.35 μg/cm2) and C (8.34 ± 0.56 and 8.61 ± 0.71 μg/cm2), respectively. Lipid permeation from formulations A and B (13.91 ± 0.26 and 12.94 ± 0.59 μg/cm2 respectively for 1.0 kcal/mL formulation, and 13.31 ± 0.21 and 12.86 ± 0.16 for 1.5 kcal/mL formulation) which consist mainly of medium chain triglycerides (MCTs), were significantly (p <0.05) higher than those from formulation C (11.49 ± 0.43 and 12.62 ± 0.38 μg/cm2 for 1.0 and 1.5 kcal/mL formulation, respectively) which mostly contained long chain triglycerides (LCTs).Conclusion: The results reveal that oligomeric formulations have higher absorption rate than polymeric formulations. However, the outcomes when administered to clinically ill patients need to be investigated.Keywords: Nutrient Formulations, Permeation, Proteins, Lipids, Porcine Intestine, Medium Chain Triglycerides, Long Chain Triglyceride

Development of Alginate/Chitosan Microparticles for Dust Mite Allerge

Purpose: To develop chitosan/alginate microparticles for the mucosal delivery of allergen from dust mite (Dermatophagoides pteronyssinus).Methods: Chitosan/alginate microparticles were prepared by ionotropic gelation. The effects of polymer content, crosslinking agent, and preparation method on the physicochemical characteristics of the microparticles as well as their in vitro cytotoxicity were investigated.Results: The microparticles were small (1 - 17 μm) and spherical in shape. The highest allergen content (0.30 ± 0.07 mg/g) was obtained with 2.5 % initial allergen loading in chitosan- triphosphate (CS-TPP) microparticles. Sustained allergen release (approx. 50 % over 24 h) was observed from alginate-coated chitosan microparticles. Allergen incorporation method and initial drug-loading could be varied to obtain optimum particle size with high allergen-loading and sustained release. The cytotoxicity of various microparticle formulations did not differ significantly (p > 0.05 ), as cell viability values were close to 100 %.Conclusion: This study indicates that alginate and alginate-coated chitosan microparticles are safe and can be further developed for mucosal allergen delivery.Keywords: Alginate, Chitosan, Microparticle, Allergen delivery, Dust mite, Dermatophagoides pteronyssinu

Mucoadhesive maleimide-functionalised liposomes for drug delivery to urinary bladder

Intravesical drug administration is used to deliver chemotherapeutic agents via a catheter to treat bladder cancer. The major limitation of this treatment is poor retention of the drug in the bladder due to periodic urine voiding. In this work, maleimide-functionalised PEGylated liposomes (PEG-Mal) were explored as mucoadhesive vehicles for drug delivery to the urinary bladder. The retention of these liposomes on freshly excised porcine bladder mucosa in vitro was compared with conventional liposomes, PEGylated liposomes, two controls (dextran and chitosan), and evaluated through Wash Out50 (WO50) values. PEG-Mal liposomes exhibited greater retention on mucosal surfaces compared to other liposomes. The penetration abilities of conventional, PEG-Mal-functionalised and PEGylated liposomal dispersions with encapsulated fluorescein sodium into the bladder mucosa ex vivo were assessed using a fluorescence microscopy technique. PEGylated liposomes were found to be more mucosa-penetrating compared to other liposomes. All liposomes were loaded with fluorescein sodium salt as a model drug and the in vitro release kinetics was evaluated. Longer drug release was observed from PEG-Mal liposomes

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

In Vitro Antioxidant Activity of Chitosan Aqueous Solution: Effect of Salt Form

Purpose: To investigate the effect of salt form on the antioxidant activities of chitosan aqueous solution.Methods: The antioxidant activities of chitosan acetate (CS-acetate), chitosan hydroxybenzotriazole (CS-HOBt), chitosan thiamine pyrophosphate (CS-TPP) and chitosan ethylenediaminetetraacetic acid (CS-EDTA) solution were determined employing various established in vitro system such as superoxide and hydroxyl radicals scavenging, metal ion chelating and reducing power. Their chemical structures were characterized by nuclear magnetic resonance (NMR) and Fourier transform infraredspectrophotometry (FT-IR).Results: NMR and FT-IR show confirmed formation of chitosan salts. The 50 % inhibition concentration (IC50) of superoxide and hydroxyl radicals was 0.349 – 1.34 and 0.34 – 1.54 mg/mL, respectively. Among the salt forms, CS-acetate (IC50 = 0.349 mg/mL) showed the highest superoxide radical scavenging effect while CS-HOBt (IC50 = 0.34 mg/mL) showed the highest hydroxyl radical scavenging effect. With regard to metal ion chelating activity, CS-EDTA showed the highest chelating activity (approx 100 % at 1 mg/mL) while the others showed 20 % activity at a concentration of 1 mg/mL. The results for reducing power indicate that CS-TPP had the highest reducing power.Conclusion: The results indicate that antioxidant activity varied with the salt form. Thus, CS salts may be used as a source of antioxidants for pharmaceutical applications.Keywords: Chitosan, Antioxidant, Hydroxybenzotriazole, Thiamine pyrophosphate, Ethylenediaminetetraacetic aci

Development and Evaluation of Ketoprofen Acrylic Transdermal Patches

Purpose: To fabricate ketoprofen transdermal patches (KTPs) using an acrylic pressure-sensitive adhesive (PSA) polymer.Methods: KTPs were prepared using solvent casting method. The influence of the amount of PSA, drug content, and terpenes as penetration enhancers on the characteristics of the patch, namely, thickness, W/A ratio, and adhesiveness and in vitro skin permeation, were investigated. Scanning electron microscope (SEM) and differential scanning calorimetry (DSC) studies were also performed on the patches. The physical and chemical stability of KTPs after storage at 40 oC, and 75 %RH for 1 month was also evaluated.Results: DSC thermograms demonstrate that the drug was dispersed molecularly in the polymer in all the formulations. Increase in PSA content increased the W/A ratio and adhesiveness of KTPs. Ketoprofen release from the transdermal patches followed the Higuchi diffusion model. Ketoprofen flux increased with increase in the ketoprofen content of the adhesive matrix. Inclusion of terpenes in the patch formulations significantly increased the permeation of ketoprofen through the skin, with enhancement ratio (ER) ranging from 1.4 to 2.6.Conclusion: KTPs formulated with acrylic pressure-sensitive adhesive and incorporating terpenes as permeation enhancers demonstrated suitable characteristics for transdermal delivery of ketoprofen.Keywords: Ketoprofen, Transdermal patch, Skin permeation, Acrylic matrix, Terpenes, Pressuresensitive adhesive

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

Fabrication of Cationic Exchange Polystyrene Nanofibers for Drug Delivery

Purpose: To prepare polystyrene nanofiber ion exchangers (PSNIE) with surface cation exchange functionality using a new method based on electrospinning and also to optimize crosslinking and sulfonation reactions to obtain PSNIE with maximum ion exchange capacity (IEC).Method: The nanofibers were prepared from 15% w/v polystyrene solution in dimethylacetamide (DMAc) containing 0.025 %w/v tetrabutylammonium bromide (TBAB) using electrospinning technique, followed by crosslinking with sulfuric acid/formaldehyde in a ratio ranging from 100/0 to 50/50 v/v and sulfonation in sulfuric acid. Degree of crosslinking was determined as the amount of fibers that remained in dichloromethane. The morphology and diameter of the fibers were evaluated by scanning electron microscopy (SEM) while IEC of PSNIE was performed by salt splitting titration.Results: PSNIE crosslinked with a sulfuric acid/formaldehyde ratio of 90/10 with 0.1 %w/v silver sulfate for 10 min at 70°C and sulfonated in 98 % sulfuric acid with 0.2 %w/v silver sulfate as the catalyst at 100°C for 30 min showed a maximum IEC of 3.21 meq/g-dry-PSNIE. Increase in  sulfonation temperature caused the IEC of PSNIE to increase due to faster sulfonation. It was observed that the higher the temperature the faster the rate of sulfonation reaction. The diameter of the fibers after sulfonation was 404 ± 42 nm.Conclusion: These results indicate that PSNIE can be successfully prepared by electrospinning. Furthermore, cationic drug can be loaded onto the novel PSNIE for controlled release delivery.Keywords: Polystyrene, Ion exchange capacity, Nanofibers, Ion exchangers, Crosslinking, Sulfonation

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