Bhavesh D. Kevadiya

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.

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.

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.

Biodegradable gelatin–ciprofloxacin–montmorillonite composite hydrogels for controlled drug release and wound dressing application

This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property.

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; VB1) and pyridoxine hydrochloride (Vitamin B6; VB6) seems to be a feasible alternative to existing therapy. The vitamins (VB1/VB6) intercalated in montmorillonite (MMT) and intercalated VB1/VB6-MMT hybrid is further used for synthesis of VB1/VB6-MMT-alginate nanocomposite beads by gelation method and in vitro release in the intestinal environment. The structure and surface morphology of the synthesized VB1/VB 6-MMT hybrid, VB1/VB6-alginate and VB1/VB 6-MMT-alginate nanocomposite beads were characterized by XRD, FT-IR, TGA and SEM. In vitro release experiments revealed that the VB1/VB 6 releases suddenly from VB1/VB6-MMT hybrid and is pH dependent. The controlled release of VB1/VB6 from VB1/VB6-MMT-alginate nanocomposite beads was observed to be controlled as compared to their release from VB1/VB 6-MMT hybrid and VB1/VB6-alginate beads.

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.

Montmorillonite-alginate composites as a drug delivery system: Intercalation and In vitro release of diclofenac sodium

Diclofenac sodium and alginate was intercalated into montmorillonite to form uniform sized beads by gelation method. The structure and surface morphology of the synthesized composite beads were characterized by powdered X-ray diffraction, Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning electron microscopy. Diclofenac release kinetics of the composite in simulated intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in vitro release of diclofenac from diclofenac-montmorillonite-alginate composites bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation efficiency in the montmorillonite-alginate composites bead increases with an increase in the montmorillonite content. The control release of diclofenac from diclofenac-montmorillonite-alginate composites beads was observed to be better as compared to diclofenac-alginate beads.

Template free synthesis of mesoporous hectorites: efficient host for pH responsive drug delivery.

The organized mesoporous matrices with large surface area and large pore volumes are potential drug carriers and hence find good applications in the field of controlled and sustained drug delivery. Two novel mesoporous synthetic hectorite (MSH) materials, namely, MSH3 and MSH4 with diverse composition and pore performance have been synthesized by a template free route and studied for the controlled drug delivery applications. MSH3 with 0.14LiF:5.93Mg(OH)2:8 SiO2 synthetic composition exhibited higher quinine adsorption than that by MSH4 (2.8LiF:4.6Mg(OH)2:8SiO2). In vitro studies at 37±0.5°C temperature under sequential buffer conditions showed controlled drug release with respect to the variation in pH values while following Eudragit VR L100 coated gelatin capsules; however, dialysis bag technique do not show such pH controlled delivery. Kinetic data suggest the release of QUI from the nanocomposite follows dissolution diffusion model.

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.

The Layered Silicate, Montmorillonite (MMT) as a Drug Delivery Carrier

Controlled drug delivery system is a protocol to develop nanostructures and materials that can efficiently encapsulate drugs at high concentration, cross the cell membrane, and release the drug at the target site in a controlled manner for a prescribed period of time. This system can reduces the patient expenses, and risks of toxicity, while it can increase the drug efficacy, specificity, tolerability and therapeutic index of corresponding drugs. Therefore, construction of stimuli-responsive controlled-release systems is of crucial importance for the development of both fundamental science and clinical medicine. Both natural and synthetic materials have been tested and proposed as components of controlled drug delivery. Clay minerals, synthetic or natural, are an important, widely abundant, and low-cost class of materials with unique swelling, intercalation, adsorption, and ion-exchange properties. The safety proof data of clay minerals clearly suggest them to be non-toxic for transdermal application and oral administration. To accomplish controlled-release systems based on layered clay minerals, one of the best ways is to intercalate organic molecules into the interlayer gallery of clay minerals. Intercalation of organic molecules within the gallery of layered silicates offers a novel route to prepare organic and inorganic hybrids that contain properties of both the inorganic host and organic guest in a single material. In this article we will highlight the applications of clay in pharmaceutics as controlled drug delivery carrier.