Controlled release formulation of ranitidine-containing montmorillonite and Eudragit E-100.

AIM: The objective of this work was to illustrate the suitability of montmorillonite (MMT) as a drug delivery carrier, by developing a new clay-drug composite of ranitidine hydrochloride (RT) intercalated in MMT. METHODS: The MMT-RT composite was prepared by ion-exchange process. X-ray diffraction and Fourier transform infrared spectra were employed to confirm the intercalation of RT in the MMT interlayers. The prepared MMT-RT hybrid was coated with cationic polymer Eudragit E-100 by oil-in-water solvent evaporation method. The release processes of RT from MMT-RT and MMT-RT/Eudragit E-100 were monitored under in vitro condition in the gastric fluid. RESULTS: X-ray diffraction and Fourier transform infrared spectra analysis indicated the intercalation of RT molecules within the clay lattice. The in vitro release studies showed that MMT-RT released RT in a controlled manner. In the case of MMT-RT/Eudragit E-100, both the release rate and the release percentages noticeably increased in the presence of Eudragit E-100, because of its effective exchange with intercalated RT molecules. The release kinetics followed parabolic diffusion mechanism. CONCLUSION: MMT has great potential as a drug delivery carrier with various scenarios. The dosage of the MMT-RT/Eudragit E-100 can be in the tablet form. The hybrid material and polymer-coated hybrids are microparticles.

Montmorillonite/poly-(ε-caprolactone) composites as versatile layered material: reservoirs for anticancer drug and controlled release property.

This work evaluates intercalation of tamoxifen (Tmx) in interlayer gallery of Na(+)-MMT (Montmorillonite, MMT) (Tmx-MMT), which is further compounded with poly-(ε-caprolactone) (PCL) (Tmx-MMT/PCL, MPs), for oral chemotherapy of breast cancer. The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the intercalation of Tmx into the MMT interlayer that stabilized in the longitudinal monolayer mode by electrostatic interaction. No significant change in structural and functional properties of Tmx was found in the MMT layers. In vitro study of drug release profiles showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated moderate reduction in DNA damage when pristine Tmx was intercalated with MMT and formulated in composites. The Tmx-MMT hybrid efficacy was also confirmed on HeLa and A549 cancer cells by in vitro cell viability assay. In vivo pharmacokinetics (PK) of formulated Tmx in rats was examined and the results showed that plasma Tmx levels were within therapeutic window as compared to pristine Tmx. Therefore, Tmx-MMT hybrid and microcomposite particles (MPs) can be of considerable value in chemotherapy of malignant neoplastic disease with reduced side effects. This study clearly indicated that MMT not only plays a role as a delivery matrix for drug, but also facilitates significant increase in the delivery proficiency.

Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU).

We report here the intercalation of 5-fluorouracil (5-FU), an anticancer drug in interlayer gallery of Na(+) clay (Montmorillonite, MMT), with the assistance of biopolymer (chitosan, CS). The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the drug intercalation into the clay interlayer space in support of CS and stabilized in the longitudinal monolayer by electrostatic interaction. In vitro drug release showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated significant reduction in DNA damage when drug was intercalated with clay and formulated in composites. The results of in vitro cell viability assay in cancer cells pointed at decreased toxicity of drug when encapsulated in Na(+)-clay plates than the pristine drug. In vivo pharmacokinetics, biodistribution, hepatotoxicity markers, e.g., SGPT and SGOT, and liver/testicular histology in rats showed plasma/tissue drug levels were within therapeutic window as compared to pristine drug. Therefore, drug-clay hybrid and composites can be of considerable value in chemotherapy of cancer with reduced side effects.

Layered bionanocomposites as carrier for procainamide.

The study deals with the intercalation of procainamide hydrochloride (PA), an antiarrythmia drug in montmorillonite (MMT), as a new drug delivery device. Optimum intercalation of PA molecules within the interlayer space of MMT was achieved by means of different reaction conditions. Intercalation of PA in the MMT galleries was conformed by X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), and thermal analysis (DSC). In order to retard the quantity of drug release in the gastric environment, the prepared PA-MMT composite was compounded with alginate (AL), and further coated with chitosan (CS). The surface morphology of the PA-MMT-AL and PA-MMT-AL-CS nanocomposites beads was analyzed by scanning electron microscope (SEM). The in vitro release experiments revealed that AL and CS were able to retard the drug release in gastric environments, and release the drug in the intestinal environments with a controlled manner. The release profiles of PA from composites were best fitted in Higuchi kinetic model, and Korsmeyer-Peppas model suggested diffusion controlled release mechanism.

Montmorillonite-alginate nanocomposites as a drug delivery system: intercalation and in vitro release of vitamin B1 and vitamin B6.

Sustained intestinal delivery of thiamine hydrochloride (Vitamin B(1); VB(1)) and pyridoxine hydrochloride (Vitamin B(6); VB(6)) seems to be a feasible alternative to existing therapy. The vitamins (VB(1)/VB(6)) intercalated in montmorillonite (MMT) and intercalated VB(1)/VB(6)-MMT hybrid is further used for synthesis of VB(1)/VB(6)-MMT-alginate nanocomposite beads by gelation method and in vitro release in the intestinal environment. The structure and surface morphology of the synthesized VB(1)/VB(6)-MMT hybrid, VB(1)/VB(6)-alginate and VB(1)/VB(6)-MMT-alginate nanocomposite beads were characterized by XRD, FT-IR, TGA and SEM. In vitro release experiments revealed that the VB(1)/VB(6) releases suddenly from VB(1)/VB(6)-MMT hybrid and is pH dependent. The controlled release of VB(1)/VB(6) from VB(1)/VB(6)-MMT-alginate nanocomposite beads was observed to be controlled as compared to their release from VB(1)/VB(6)-MMT hybrid and VB(1)/VB(6)-alginate beads.

Montmorillonite as a drug delivery system: intercalation and in vitro release of timolol maleate.

The need for safe, therapeutically effective, and patient-compliant drug delivery systems continuously leads researchers to design novel tools and strategies. Clay minerals play a very crucial role in modulating drug delivery. This work examines the advantageous effect of clay mineral as drug carrier for timolol maleate (TM), a nonselective beta-adrenergic blocking agent. The intercalation of TM into the interlayer of montmorillonite (MMT) at different pH and initial concentration is demonstrated. MMT-TM hybrid was characterized by X-ray diffraction (XRD), Fourier transformed infrared (FT-IR), and thermal analysis (TG-DTA). TM was successfully intercalated into the interlayer of MMT, and in vitro release properties of the intercalated TM have been investigated in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.4) at 37+/-0.5 degrees C. Controlled release of TM from MMT-TM hybrid has been observed during in vitro release experiments.