Mont Kumpugdee-Vollrath

Spontaneous Emulsification of Nifedipine-Loaded Self-Nanoemulsifying Drug Delivery System

ABSTRACTSelf-nanoemulsifying drug delivery system (SNEDDS) can be used to improve dissolution of poorly water-soluble drugs. The objective of this study was to prepare SNEDDS by using ternary phase diagram and investigate their spontaneous emulsifying property, dissolution of nifedipine (NDP), as well as the pharmacokinetic profile of selected SNEDDS formulation. The results showed that the composition of the SNEDDS was a great importance for the spontaneous emulsification. Based on ternary phase diagram, the region giving the SNEDDS with emulsion droplet size of less than 300 nm after diluting in aqueous medium was selected for further formulation. The small-angle X-ray scattering curves showed no sharp peak after dilution at different percentages of water, suggesting non-ordered structure. The system was found to be robust in different dilution volumes; the droplet size was in nanometer range. In vitro dissolution study showed remarkable increase in dissolution of NDP from SNEDDS formulations compared with NDP powders. The pharmacokinetic study of selected SNEDDS formulation in male Wistar rats revealed the improved maximum concentration and area under the curve. Our results proposed that the developed SNEDDS formations could be promising to improve the dissolution and oral bioavailability of NDP.

Increasing Solubility of Poorly Water Soluble Drug Resveratrol by Surfactants and Cyclodextrins

Resveratrol (Res) is a polyphenolic secondary natural substance and can be used as anti-inflammatory, anti-aging, anti-heart disease and anti-cancer agent. However, Res has low water solubility which causes a low bioavailability in human body. In order to increase solubility we have prepared different inclusion complexes with native ((α, β, γ) and modified (2-hydroxypropyl-beta, dimethyl-beta) cyclodextrins (Cd) as well as solid dispersions using several surfactants (Imwitor 742, Imwitor 928, PEG 6000, Span 40, Span 60, Solutol HS15) with Res. The solubility of all mixtures was determined by UV-VIS spectroscopy at the wavelength of 305 nm. Regarding the Cd, the complex of Res with 2-hydroxypropyl-beta-Cd at a ratio of 1:3 showed the highest water solubility (248210 g/l). Concerning the surfactants, the solid dispersion from Res and Solutol HS15 showed the highest water solubility (16140 g/l). The complexation and the solid dispersion phase were confirmed by DSC. The results will be a basis for better formulation of resveratrol with higher bioavailability.

Determination of nanostructure of liposomes containing two model drugs by X-ray scattering from a synchrotron source.

Small-angle X-ray scattering has been employed to study how the introduction of paracetamol and acetylsalicylic acid into a liposome bilayer system affects the systems nanostructure. An X-ray scattering model, developed for multilamellar liposome systems [Pabst et al. (2000), Phys. Rev. E, 62, 4000-4009], has been used to fit the experimental data and to extract information on how structural parameters, such as the number and thickness of the bilayers of the liposomes, thickness of the water layer in between the bilayers, size and volume of the head and tail groups, are affected by the drugs and their concentration. Even though the experimental data reveal a complicated picture of the drug-bilayer interaction, they clearly show a correlation between nanostructure, drug and concentration in some aspects. The localization of the drugs in the bilayers is discussed.

An Abraded Surface of Doxorubicin-Loaded Surfactant-Containing Drug Delivery Systems Effectively Reduces the Survival of Carcinoma Cells

An effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next-generation drugs. We used doxorubicin (Dox) liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small-angle X-ray scattering (SAXS) measurements. SAXS measurements revealed that Dox-loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil-containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox-loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next-generation drug carrier systems using structural insights to guide the development of next-generation drug delivery systems with increased efficacy and reduced side effects.

Behaviour of Lipid-Based Formulations Containing Nifedipine in Aqueous Media as Observed by Small Angle X-Ray Scattering

Lipid-based formulations (LBF) including self-emulsifying drug delivery system have been used to improve drug dissolution and bioavailability by avoiding rate-limiting step during dissolution of poorly water-soluble drugs. This study was aimed to investigate the behavior of lipid-based formulations upon dilution in aqueous media by using small angle X-ray scattering (SAXS). LBF is composed of oil (caprylic/capric glyceride), surfactants (polyoxyl 35 castor oil or polyoxyl 40 hydrogenated castor oil), and co-solvent (diethylene glycol monoethyl ether) at a weight ratio of 1:1:8. Nifedipine, a poorly water-soluble drug, was used as a model drug. A 100-fold dilution of the LBF in aqueous media (i.e., simulated gastric fluid USP without pepsin (SGF) and distilled water) resulted in nanosized emulsion (less than 200 nm). The selected formulations were diluted in aqueous media at various ratios (e.g., 0.01, 0.02, 0.04, 0.06, 0.09, 0.11, 0.18, 0.25, 0.67, 1.5, 4, 99, 199 and 300 folds) and then, after equilibrium, monitored by SAXS in order to observe the surfactant rearrangement. The results from SAXS scattering curves (q of 0.027-0.980 Å-1) demonstrated that a lamellar phase or liquid crystalline was not formed upon dilution. The emulsions were formed without the ordered structure.

Chitosan-based self-assembled nanocarriers coordinated to cisplatin for cancer treatment

Polymeric nanocarriers were prepared via a dialysis method using three chitosan derivatives, N-benzyl-N,O-succinyl chitosan (BSCT), N-naphthyl-N,O-succinyl chitosan (NSCT), and N-octyl-N-O-succinyl chitosan (OSCT) and were coordinated to cisplatin. The nanocarrier properties and cytotoxicity on the human carcinoma cells, HN22 (head and neck), were investigated. In addition, intracellular cisplatin accumulation, apoptosis induction and toxicity on renal cells were also evaluated. The findings revealed that the succinyl groups of the polymers were perfectly deprotonated and bound with cisplatin by co-ordinate bonds at pH 8.5. Among the derivatives, BSCT exhibited the highest cisplatin loading and release in simulated physiological medium. The cytotoxicities on HN22 cells of cisplatin-loaded BSCT nanocarriers were lower than that of free cisplatin, however, they presented a greater percentage of early apoptosis in HN22 cells and could decrease cisplatin induced renal cell death. In conclusion, the BSCT self-assembly nanocarrier might be a cisplatin carrier for sustained release, which provides prolonged antitumour treatment and reduced nephrotoxicity.

Controlled Release of Resveratrol and Lignan by Matrix Tableting

The aim of this research work was to develop the controlled release of two model drugs i.e. water insoluble drug - resveratrol and water soluble drug - lignan by matrix tableting with an eccentric tablet machine. For this purpose different kinds of polymers i.e. Metolose 90 SH-4000® (HMPC), Fetocel RT-N-100® (EC) and Eudragit RLPO® (polymethacrylate) were used. The matrix tablets containing 2 %wt of a model drug which were mixed with 5, 10, 20, 30 and 50 %wt of the polymers mentioned above. In addition, a glidant composed of 1 %wt talc and 1 %wt magnesium stearate as well as a filler Ludipress® were processed. Different physical properties of the powder mixtures (e.g. flowability) and of the tablets (e.g. hardness, uniformity of mass or drug content, drug release, etc.) were determined. Most of the tablets met the physical requirements. If the polymer content got higher the release was slower, which can be confirmed by the lower values of k. The release kinetics were described by three typical mathematic models i.e. biphasic, Noyes-Whitney and KorsmeyerPeppas. The best fitting results were ordered as follows: biphasic > Noyes-Witney > KorsmeyerPeppas.

Interfacial and Emulsifying Behavior of Essential Oils Using as Retarded Steam Delivery

Storage behavior and controlled release of steam are the most important properties of the essential o/w emulsions for application in steam baths. The interfacial behavior, emulsion properties and steam delivery of three commercial essential oils were investigated to improve their application. A special designed lab-scale steam chamber was successfully used for the release tests. It was found that the essential oils showed characteristic interfacial and emulsion behaviors which depend on the content of surface active compounds. The relative steam delivery profile of various oil types were negligibly different. The most useful application form seems to be oil-loaded micelle dispersions (solubilisates).

Polymer Mixtures as Colon Targeted Drug Delivery Systems

For the development of colon delivery systems (CDS) formulations have to be gastric resistant. The advantage of the CDS is the ability for a local treatment for colon diseases but also its systemic action. CDS can also increase the bioavailability of poorly water soluble drugs e.g. resveratrol, which can be degraded in the upper gastrointestinal tract or by the First-Pass-Effect. In this project the coating technique with different polymer mixtures containing Kollicoat MAE-30DP, Eudragit-NM, Eudragit-L, and Eudragit-NE was investigated. Resveratrol was used as a model drug and all formulations were coated with a polymer mixture in a small scale fluidized bed apparatus. Morphology, roughness and film thickness of the coated tablets were determined by a scanning electron microscope and a 3D light microscope. Drug amount was determined by UV-spectrometry. Release studies were performed in a dissolution apparatus type II. Kinetic profiles of drug release were demonstrated. Results exhibit the advantages of polymer mixtures for CDS in comparison with results of pure Kollicoat MAE-30DP which were published in one of our latest publications.

Coatings in der pharmazeutischen Industrie

Wenn Coatings in der pharmazeutischen Industrie verwendet werden sollen, sind folgende Fragen zu beantworten: