S.V Fulzele

Study of the biodegradation and in vivo biocompatibility of novel biomaterials

The degradation of two rosin-based biomaterials, the glycerol ester of maleic rosin (GMR) and the pentaerythritol ester of maleic rosin (PMR), was examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a subcutaneous rat model. Free films of the two biomaterials with mean thickness 0.4+/-0.02 mm were used for the study. The initial biocompatibility was followed by microscopic examination of the inflammatory tissue response to the implanted films. Sample weight loss and molecular weight decline of the free films was used to monitor the degradation quantitatively, while surface morphological changes were analysed for qualitative estimation. Biocompatibility response was followed on post-operative days 7, 14, 21 and 28 and compared with those of poly(DL-lactic-co-glycolic acid) (PLGA) (50:50) films. Both biomaterials showed slow in vitro degradation when compared with the in vivo rate. The mechanism followed was, however, bulk degradation of the films. The penta-esterified form of maleic rosin was observed to degrade more rapidly than glycerol esterified maleic rosin. The acute and subacute inflammatory reactions were characterized by fibrosis at the end of 28 days. The biomaterials showed reasonable tissue tolerance to the extent evaluated. There was a total absence of tissue necrosis or abscess formation for all implanted films. The response, although not identical to that of PLGA, is reasonable, promising new drug delivery applications for rosin biomaterials.

Polymerized rosin: novel film forming polymer for drug delivery.

Polymerized rosin (PR) a novel film forming polymer is characterized and investigated in the present study for its application in drug delivery. Films were produced by a casting/solvent evaporation method from plasticizer free and plasticizer containing solutions. Films prepared from different formulations were studied for their mechanical (tensile strength, percent elongation and Youngs modulus), water vapour transmission and moisture absorption characteristics. Neat PR films were slightly brittle and posed the problem of breaking during handling. Hydrophobic plasticizers, dibutyl sebacate and tributyl citrate, improved the mechanical properties of free films with both the plasticizers showing significant effects on film elongation. Release of diclofenac sodium (model drug) from coated pellets was sustained with high coating levels. Concentration of plasticizer was found to affect the release profile. PR films plasticized with hydrophobic plasticizers could therefore be used in coating processes for the design of oral sustained delivery dosage forms.

Biodegradation and in vivo biocompatibility of rosin: a natural film-forming polymer

The specific aim of the present study was to investigate the biodegradation and biocompatibility characteristics of rosin, a natural film-forming polymer. Both in vitro as well as in vivo methods were used for assessment of the same. The in vitro degradation of rosin films was followed in pH 7.4 phosphate buffered saline at 37°C and in vivo by subdermal implantation in rats for up to 90 days. Initial biocompatibility was followed on postoperative days 7, 14, 21, and 28 by histological observations of the surrounding tissues around the implanted films. Poly (DL-lactic-co-glycolic acid) (PLGA) (50∶50) was used as reference material for biocompatibility. Rate and extent of degradation were followed in terms of dry film weight loss, molecular weight (MW) decline, and surface morphological changes. Although the rate of in vitro degradation was slow, rosin-free films showed complete degradation between 60 and 90 days following subdermal implantation in rats. The films degraded following different rates, in vitro and in vivo, but the mechanism followed was primarily bulk degradation. Rosin films demonstrated inflammatory reactions similar to PLGA, indicative of good biocompatibility. Good biocompatibility comparable to PLGA is demonstrated by the absence of necrosis or abscess formation in the surrounding tissues. The study provides valuable insight, which may lead to new applications of rosin in the field of drug delivery.

Rosin derivatives: novel film forming materials for controlled drug delivery

Abstract Two new rosin derivatives (RD-1 and RD-2) were synthesized in the laboratory and evaluated for physicochemical properties, molecular weight ( M w ), polydispersity ( M w / M n ) and glass transition temperature ( T g ). Plasticizer free films of the derivatives were produced by casting/solvent evaporation method. The surface morphology (SEM), water vapour transmission and mechanical properties (tensile strength, percent elongation and modulus of elasticity) of the films were investigated. The derivatives were further evaluated for pharmaceutical film coating by characterizing the release of a model drug (diclofenac sodium) from non-pariel seeds (pellets) coated with the derivatives. Pellet film coating could be achieved without agglomeration of the pellets within a reasonable operation time. Drug release from the coated pellets was sustained up to 10 h with the two rosin derivatives. These findings suggest the possible application of rosin derivatives (RD-1 and RD-2) for film coating.

Preparation and evaluation of microcapsules using polymerized rosin as a novel wall forming material.

Sustained release diclofenac sodium microcapsules were prepared using polymerized rosin as a novel wall-forming material by a solvent evaporation technique. A novel method developed in our laboratory with the potential for scale-up and production of polymerized rosin microcapsules is detailed. These microcapsules might have application for development of implant/depot systems, primarily due to a sustained/controlled release capability and potential biocompatibility of polymerized rosin. The effect of variables like solvent systems, stirring speed and temperature were previously optimized. The solution system of drug and polymerized rosin dissolved in iso-propyl alcohol and acetone is sprayed with the help of a 0.5 mm nozzle spray gun in liquid paraffin maintained at 60°C in the stirring condition. Varying drug:polymer ratios, namely 1:1, 1:2, 2:1, 1:3 and 3:1, were employed for microcapsule preparation. The prepared microcapsules were evaluated for size, shape, drug content and in vitro drug release. The morphology of microcapsules was characterized by scanning electron microscopy. The microcapsules show sustained release curves at pH 7.4 phosphate buffer for up to 10 h. The data obtained from the dissolution profiles were compared in the light of different kinetics models and the regression coefficients were compared. The in vitro dissolution study confirmed the Higuchi-order release pattern. Particle size and release data analysis from five consecutive batches prepared in the laboratory indicated suitable reproducibility of the proposed solvent evaporation process.

Evaluation of polymerized rosin for the formulation and development of transdermal drug delivery system: A technical note

ConclusionsResults from the present study conclude that PR in combination with PVP and with incorporation of dibutyl phthalate (30% wt/wt) produces smooth flexible films with improved tensile strength and percentage elongation. The release rate of drug from films and permeation across skin increases with increase in drug and PVP loading but is independent of film thickness. Patches containing PR:PVP (7:3) show promise for pharmacokinetic and pharmacodynamic performance evaluation in a suitable animal model. In view of the overall results reported in the present study, it may be proposed that PR can be used in the design of a matrix type transdermal drug delivery system to prolong the drug release.

Synthesis and evaluation of rosin-based polymers as film coating materials.

ABSTRACT Rosin-based polymers (R-1 and R-2) were synthesized and characterized for physicochemical properties, molecular weight (Mw), polydispersity (Mw/Mn), glass transition temperature (Tg), and thermogravimetry (TGA). Films of the polymers were cast on a mercury substrate by solvent evaporation technique. Free films were characterized for surface topography by scanning electron microscopy (SEM), water vapor transmission rate (WVTR), tensile strength, percentage elongation, and modulus of elasticity. The polymers were further evaluated as film coating materials by evaluating drug release from coated pellets with diclofenac sodium as a model drug. Drug was loaded on non-pareil seeds by a solution-layering technique and coated with varying concentrations of polymer solutions. Sustained release of the drug was observed from coated pellets. The newly synthesized rosin-based polymers promise considerable utility for pharmaceutical coating.

Biodegradation studies of rosin-based polymers.

Abstract This study was designed to investigate two rosin-based polymers (R-1 and R-2) for their in vitro and in vivo biodegradation behavior. The in vitro hydrolytic degradation was carried out in buffer solutions of pH 4.4, 7.4, and 10.4 at 37°C. Enzymatic degradation was studied using enzymes lipase, pancreatine, and pectinase. Free films of the two polymers were subcutaneously implanted in rabbits for the in vivo biodegradation. The extent of degradation was determined quantitatively by weight loss and was followed qualitatively by scanning electron microscopy. The extent and the rate of degradation was better in vivo than in vitro. The polymers showed poor enzymatic degradation and a highly pH-dependent hydrolytic degradation.

Study of novel rosin-based biomaterials for pharmaceutical coating

The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Youngs modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Youngs modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations. Diclofenac sodium-layered pellets coated with GMR and PMR film formulations showed sustained drug release for up to 10 hours. The release rate was influenced by the extent of plasticization and coating level. The results obtained in the study demonstrate the utility of novel rosin-based biomaterials for pharmaceutical coating and sustained-release drug delivery systems.

Evaluation of the film-forming property of hydrogenated rosin.

Abstract The film-forming and coating properties of a new biomaterial, hydrogenated rosin (HR), is investigated in the present communication. Films produced by casting method are studied for mechanical, (tensile strength, elongation, and Youngs modulus), water vapor transmission, and moisture absorption characteristics. Type of plasticizer and its concentration were observed to play an important role in modifying the film characteristics. Dibutyl sebacate (DBS), a hydrophobic plasticizer, was found to be suitable for development of flexible and smooth films. Film formulations plasticized with DBS were investigated for coating the drug layered nonpareil seeds where plasticization facilitated development of smooth and uniformly coated pellets. The increase in coat buildup, however, did not sustain the drug release significantly. The studies conclude that HR films promise utility as moisture-protective hydrophobic, film-coating materials.