Preparation and in vitro evaluation of meloxicam-loaded PLGA nanoparticles on HT-29 human colon adenocarcinoma cells.

CONTEXT: The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells. OBJECTIVE: In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined. METHODS: NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays. RESULTS: NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs. CONCLUSION: The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.

Ethylcellulose-based matrix-type microspheres: influence of plasticizer RATIO as pore-forming agent.

In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology, total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio of TEC.

Microsphere-based once-daily modified release matrix tablets for oral administration in angina pectoris.

The objective of this research was to develop microsphere-based once-daily modified release tablet formulations of diltiazem hydrochloride (DH), a potent calcium channel blocker used in angina pectoris. For this purpose, DH-loaded microspheres were prepared by the solvent evaporation technique using Eudragit RS 100. The effect of variation in the drug/polymer ratio on the physical and release characteristics of the microspheres was investigated. After the selection of the suitable microspheres, tablets were compressed using Compritol 888 ATO, Ludipress and Cellactose 80 as different direct tableting agents and excipients. As a result, modified release tablet formulations of DH-loaded microspheres were designed successfully for oral administration once rather than two or three times a day in angina pectoris.

Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride.

In this study, development of modified release tablet formulations containing diltiazem hydrochloride-loaded microspheres to be taken once rather than two or three times a day was attempted. For this purpose, ethylcellulose microspheres were prepared by emulsion-solvent evaporation technique. The influence of emulsifier type and drug/polymer ratio on production yield, encapsulation efficiency, particle size, surface morphology and in-vitro release characteristics of the microspheres was evaluated. Suitable microspheres were selected and tabletted using different tabletting agents, Ludipress, Cellactose80, Flow-Lac100 and excipients Compritol888 ATO, KollidonSR. Tablets were evaluated from the perspective of physical and in-vitro drug release characteristics. It was seen that type and ratio of the excipients played an important role in the tabletting of the microspheres. As a result, two tablet formulations containing 180 mg diltiazem hydrochloride and using either Compritol888 ATO or KollidonSR were designed successfully and maintained drug release for 24 h with zero order and Higuchi kinetics, respectively.

Mucoadhesive microspheres containing gentamicin sulfate for nasal administration: preparation and in vitro characterization.

In this study, suitable microsphere formulations were designed in order to provide the absorption of a high polar drug through nasal mucosa. For this purpose, gentamicin sulfate (GS) was chosen as a model drug and used at different drug/polymer ratios in the microsphere formulations. The microspheres were prepared by spray drying technique. Hydroxypropyl methylcellulose was used as a mucoadhesive polymer in the formulations to increase the residence time of the microspheres on the mucosa. Sodium cholate was added into the formulations for increasing the absorption of GS through nasal mucosa. The in vitro characteristics of the microspheres were determined. The microspheres were evaluated with respect to the particle size, production yield, encapsulation efficiency, shape and surface properties, drug-polymer interaction, mucoadhesive property, in vitro drug release and suitability for nasal drug delivery.

Preparation and in vitro evaluation of modified release ketoprofen microsponges.

Microsponges containing ketoprofen and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. The effects of different mixing speeds, drug-polymer ratios, solvent-polymer ratios on the physical characteristics of the microsponges as well as the in vitro release rate of the drug from the microsponges were investigated. All the factors studied had an influence on the physical characteristics of the microsponges. In vitro dissolution results showed that the release rate of ketoprofen was modified in all formulations.

The effects of pressure and direct compression on tabletting of microsponges.

Microsponges are porous, polymeric microspheres that are used mostly for topical and recently for oral administration. Ketoprofen was used as a model drug for systemic drug delivery of microsponges in the study. Ketoprofen microsponges were prepared by quasi-emulsion solvent diffusion method with Eudragit RS 100 and afterwards tablets of microsponges were prepared by direct compression method. Different pressure values were applied to the tablet powder mass in order to determine the optimum pressure value for compression of the tablets. Results indicated that microsponge compressibility was much improved over the physical mixture of the drug and polymer and owing to the plastic deformation of sponge-like structure, microsponges produce mechanically strong tablets.