Drug Diffusion Properties Research Articles

COMPARATIVE STUDY OF SPAN 40 AND SPAN 60 BASED SOY-GELS FOR TOPICAL DRUG DELIVERY

Objective: Hydrogels or emulgels are recommended for topical application to elicit a local effect. However, they suffer from stability problems. The present study deals with the formulation and comparison of thermally stable soybean oil-based novel topical organogels (soy-gels) using two different gelators (Span 40 and Span 60) for controlled drug delivery.
 Methods: Soy-gels (8 batches) were developed with Span 40 and Span 60 by solid fiber mechanism and characterized for viscosity, gelation kinetics behavior, gel-sol transition parameters, drug content, in vitro drug release pattern, and changes occurring during accelerated thermal stability studies.
 Results: Fourier transformed infrared spectroscopic confirmed the compatibility among the organogel components and paracetamol. The formulations exhibited skin and hemocompatibility. The viscosity of Span 60 based soy-gels was found to be approximately 10 times higher than those of Span 40 based formulations. In comparison to Span 40, Span 60 induced faster gelation (3–6 min) of soybean oil at lower concentration (16% w/v) forming less flexible but thermally more stable soy-gels demonstrating higher Tg values. Higher flexibility and lower viscosity accounted for improved drug diffusion (both Fickian and non-Fickian) from Span 40 gels of varying concentrations in pH 5.8. However, zero-order drug release was observed in organogel with 18% w/v Span 40 only and all Span 60-based formulations except the one with 22% w/v Span 60. Non-Fickian drug diffusion occurred from Span 60 based soy-gels. A gradual increase in gelation time was observed until five cycles of freeze-thaw.
 Conclusion: Therefore, the choice of organogelator governs the rheological, thermal, and drug diffusion properties of soy-gels intended for topical application.

Magnetic field responsive methylcellulose-polycaprolactone nanocomposite gels for targeted and controlled release of 5-fluorouracil

ABSTRACT5-Fluorouracil loaded magnetic field sensitive methylcellulose and polycaprolactone gels were prepared and characterized by FTIR, XRD, TGA, SEM, and VSM. Swelling analysis supplied important information on drug diffusion properties. The release profile of gels was investigated in different buffer solutions and the highest release values were observed at pH = 7.2. Release kinetic was analyzed using an empirical equation to clarify the transport properties of drug. The effects of nanoparticle concentration and applying external magnetic field were investigated on release profile. The results indicated that the drug release decreased by both, applying external magnetic field and increasing the concentration of Fe3O4 nanoparticles.

Preparation and evaluation of the effect of particle size on the properties of chitosan-montmorillonite nanoparticles loaded with isoniazid

In this report, efforts have been made to develop isoniazid loaded chitosan-montmorillonite nanoparticles by ionic gelation of chitosan with pentasodium tripolyphosphate. The nanoparticles have been characterized by FTIR, XRD, SEM and TEM. The effect of surfactant and particle size on chitosan nanoparticles have been assessed with regard to swelling, encapsulation efficiency and release of isoniazid in different mediums. Swelling experiments provide important information on drug diffusion properties, which indicates that the chitosan nanoparticles are highly sensitive to the pH environment. The drug release mechanism has been studied during different time periods using a UV-visible spectrophotometer. Cytotoxicity has been assessed by MTT assay analysis. Mucoadhesion properties have been appraised by an in vitro wash off test and an ex vivo mucoadhesion test. The results imply that chitosan-montmorillonite nanoparticles can be exploited as potential drug carriers for controlled-release applications.

Physicochemical and drug diffusion analysis of rifampicin containing polyethylene glycol–poly(ɛ-caprolactone) networks designed for medical device applications

This study reports the physicochemical and drug diffusion properties of rifampicin containing poly(ɛ-caprolactone) (PCL)/polyethylene glycol (PEG) networks, designed as bioactive biomaterials. Uniquely, the effects of the states of both rifampicin and PEG and the interplay between these components on these properties are described. PCL matrices containing rifampicin (1–5%, w/w) and PEG 200 (0–15%, w/w) were prepared by casting from an organic solvent (dichloromethane). The films were subsequently characterized in terms of their thermal/thermorheological, surface and tensile properties, biodegradation and drug diffusion/release properties. Incorporation of PEG and/or rifampicin significantly affected the tensile and surface properties of PCL, lowering the ultimate tensile strength, % elongation at break, Young modulus and storage and loss moduli. Both in the absence and presence of PEG, solubilisation of rifampicin within the crystalline domains of PCL was observed. PEG was present as a dispersed liquid phase. The release of rifampicin (3% loading) was unaffected by the presence of PEG. Similarly the release of rifampicin (5%) was unaffected by low concentrations of PEG (5–10%) however, at higher loadings, the release rate of rifampicin was enhanced by the presence of PEG. Rifampicin release (10% loading) was enhanced by the presence of PEG in a concentration dependent fashion. These observations were accredited to enhanced porosity of the matrix. In all cases, diffusion-controlled release of rifampicin occurred which was unaffected by polymer degradation. This study has uniquely illustrated the effect of hydrophilic pore formers on the physicochemical properties of PCL. Interestingly, enhanced diffusion controlled release was only observed from biomaterials containing high loadings of PEG and rifampicin (5, 10%), concentrations that were shown to affect the mechanical properties of the biomaterials. Care should therefore be shown when adopting this strategy to enhance release of bioactive agents from biomaterials.

Preparation and Evaluation of Tubular Micelles of Pluronic Lecithin Organogel for Transdermal Delivery of Sumatriptan

The present work focuses on the preparation and evaluation of lecithin organogel system of thermoreversible polymer pluronic F127, which would enhance the stability and absorption of sumatriptan succinate across the skin. Formulations were developed with and without co-surfactant (pluronic F127). The prepared organogels were evaluated for its appearance, organoleptic characteristics, and feel upon application, homogeneity, occlusivenes, washability, pH, viscosity, spreadability, gel transition temperature of formulations. The formulations were also evaluated for drug content, in vitro drug diffusion properties and skin irritation testing. In vivo evaluation of formulations was carried out by hot plate and writhing test method, and finally the optimized formulation was subjected to stability studies. The developed formulations were easily washable, smooth in feel, and showed no clogging which indicate superior texture of system. Formulation, containing pluronic showed greater spreadability and higher drug diffusion rate as compared to pluronic free organogel. Drug content of organogel formulations was in the range of 94-97%. The pH of the formulations was 6.48 ± 0.5 and 6.98 ± 0.1, reflecting no risk of skin irritation. Pluronic not only enhances the stability of organogel by increasing the viscosity (from 6,541 ± 234.76 to 7,826 ± 155.65 poise) but also increases the release of drug from 67.39 ± 1.53% to 74.21 ± 1.7%. The sumatriptan exhibits higher and long lasting antinociceptive effect as indicated by the persistent increase in reaction time in hot plate and inhibited abdominal contraction in acetic acid-induced writhing test (p < 0.05). The prepared optimized formulation was found to be stable without any significant changes at room temperature.

Controlled release of chlorpheniramine maleate through IPN beads of sodium alginate‐g‐methylmethacrylate

AbstractControlled release of chlorpheniramine maleate drug, through sodium alginate‐g‐methylmethacrylate (NaAlg‐g‐MMA) interpenetrating polymeric network beads, has been investigated. Beads were prepared by precipitating the viscous solution of NaAlg‐g‐MMA in acetone followed by cross‐linking with glutaraldehyde. The beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Different formulations of beads were developed by varying amounts of MMA, cross‐linking agent, and drug concentration. DSC thermograms of chlorpheniramine maleate drug‐loaded NaAlg‐g‐MMA beads confirmed the molecular level distribution of drug in the polymer matrix. FTIR of beads confirm the grafting and cross‐linking, SEM of the beads suggested the formation of spherical particles. Swelling experiments on the beads provided an important information on drug diffusion properties. Release data have been analyzed using an empirical equation to understand the nature of transport of drug containing solution through the polymeric matrices. The controlled release characteristics of the matrices for chlorpheniramine maleate was investigated in pH 7.4 media. Drug was released in a controlled manner upto 12 h. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Extended release of a large amount of highly water-soluble diltiazem hydrochloride by utilizing counter polymer in polyethylene oxides (PEO)/polyethylene glycol (PEG) matrix tablets

The purpose of this study was to evaluate the feasibility of using a counter polymer in polyethylene oxide (PEO)/polyethylene glycol (PEG) polymeric matrices for the sustained release of a large amount of highly water-soluble drug. PEO/PEG matrix tablets (CR-A) containing four drugs with different water solubilities were prepared to investigate the effect of drug solubility on the drug-release and diffusion properties of PEO/PEG matrices. Cross-linked carboxyvinyl polymer (CVP)/PEO/PEG matrix tablets (CR-B) containing a water-soluble drug, diltiazem hydrochloride (DTZ), were also prepared, and their in vitro characteristics were compared with those of CR-A. Their in vitro drug release properties were evaluated using a dissolution test, and the polymeric erosion and drug diffusion properties of the matrices were also calculated. Drugs with higher solubility in water were released faster for the CR-A. The drug-release rate also increased with the amount of drug loaded. CR-A containing 50% DTZ (by weight) extended drug release by only 6 h. This confirms the difficulty experienced when trying to formulate PEO/PEG matrices for the sustained release of a large amount of highly water-soluble drugs due to large drug diffusion. In an attempt to control this issue, a polymer bearing a charge opposite that of the drug was used to effectively decrease the diffusion of DTZ, resulting in sustained release for 24 h or longer. These results suggested that including counter polymer in the PEO/PEG matrix tablet is a useful tool for achieving the sustained release of a large amount of highly water-soluble drug.

PH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: Swelling and in vitro drug release

Novel polyelectrolyte hydrogels (coded as GA) based on cationic guar gum (CGG) and acrylic acid monomer by photoinitiated free-radical polymerization were synthesized with various feed compositions. Fourier transform infrared spectra (FTIR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) confirmed that the formation of the polyelectrolyte hydrogels was attributed to the strong electrostatic interaction between cationic groups in CGG and anionic groups in poly (acrylic acid) (PAA). Swelling experiments provided important information on drug diffusion properties, which indicated the GA hydrogels were highly sensitive to pH environments. Potential applications of the hydrogels matrices in controlled drug delivery were also examined. The ketoprofen-loaded CGG/PAA matrices were prepared by hydrogels and directly compressed tablets, respectively. Release behavior of ketoprofen relied on the preparative methods of matrices, ratios of CGG/AA and pH environments. The release mechanism was studied by fitting experimental data to a model equation and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in pH 7.4 buffer solution was mainly non-Fickian diffusion. However, for tablets, the drug release in pH 7.4 buffer solution was mainly affected by polymer erosion. The pH of the dissolution medium appeared to have a strong effect on the drug transport mechanism. At more basic pH values, Case II transport was observed, indicating a drug release mechanism highly influenced by macromolecular chain relaxation. The ketoprofen release is also tested in the conditions chosen to simulate gastrointestinal tract conditions. The results implied that the GA hydrogels can be exploited as potential carriers for colon-specific drug delivery.

Preparation of sodium alginate–methylcellulose blend microspheres for controlled release of nifedipine

Carbohydrate polymeric blend microspheres, consisting of sodium alginate (NaAlg) and methylcellulose (MC) were prepared by water-in-oil (W/O) emulsion method. These microspheres were cross-linked with glutaraldehyde and loaded with nifedipine (NFD), an anti-inflammatory drug. The microspheres were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and laser particle size analyzer. DSC thermograms of NFD-loaded NaAlg–MC microspheres confirmed the molecular level distribution of NFD in the polymer matrix. SEM picture of the microspheres suggested the formation of spherical particles. Swelling experiments on the microspheres provided important information on drug diffusion properties. Release data have been analyzed using an empirical equation to understand the nature of transport of drug containing solution through the polymeric matrices. The controlled release characteristics of the matrices for NFD were investigated in pH 7.4 media. Particle size and size distribution of the microspheres was studied by laser light diffraction particle size analyzer. Drug was released in a controlled manner up to 12 h.

Novel chitosan-based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil

This paper addresses development of novel pH-sensitive interpenetrating polymeric network (IPN) microgels (MGs) based on chitosan, acrylamide- grafted-poly(vinyl alcohol) and hydrolyzed acrylamide- grafted-poly(vinyl alcohol) that are crosslinked with glutaraldehyde and used in the controlled release (CR) of cefadroxil, an antibiotic drug. The MGs formed were characterized by Fourier transform infrared spectroscopy to confirm the grafting and crosslinking reaction, scanning electron microscopy to understand the surface morphology and differential scanning calorimetry to conform a uniform distribution of the drug in the polymer matrix. Swelling experiments on hydrogels provided important information on drug diffusion properties. In vitro release results performed in acidic and basic media affected the drug release characteristics. Release data have been analyzed using an empirical equation to understand about the transport of drug containing solution through the polymeric matrices. Extent of crosslinking was studied in terms of size of MGs as well as their release characteristics. Effect of drug loading on encapsulation efficiency was investigated to find a linear manner. IPN matrices of this study were able to extend the release rates from conventional dosage release times to more than 10 h.

Use of a Novel Modified TSI for the Evaluation of Controlled-Release Aerosol Formulations. I

When considering the development of potential controlled-release pulmonary drug delivery systems, there is at present no standard method available for the assessment of in vitro drug release profiles necessary to understand how the drug might release following deposition in the lungs. For this purpose, the twin-stage impinger (TSI), apparatus A of the BP, has been redesigned and tested. This modified TSI was found capable of discriminating between drug release rates from conventional and different dry powder formulations consisting of model controlled-release excipients, providing information related to (a) drug diffusion properties of controlled-release dry powder blends with different excipient components and (b) the effect of varying drug concentration within a given formulation.

Effect of presence and type of lipophilic compound on the in vitro diffusion of clonazepam from hydrophilic ointment bases

The effect was investigated of adding to the vehicle three different kinds of lipid compounds (lauryl alcohol, isopropylmiristate or vaseline oil) on the release of clonazepam from hydrophilic ointment bases. Diffusion experiments were carried out using artificial cellulose nitrate membranes impregnated with these lipid products. The importance of the type of lipophilic substance in promoting or decreasing drug diffusion properties was shown. Lauryl alcohol proved to be the best enhancer of drug release and permeation.