S. B. Joshi

Gum copal and gum damar: Novel matrix forming materials for sustained drug delivery

This study concerns the evaluation of natural gum copal and gum damar as novel sustained release matrix forming materials in tablet formulation. Along with the physicochemical properties, gum copal and gum damar were characterized for molecular weight, polydispersity index and glass transition temperature. Matrix tablets were prepared by wet granulation technique using isopropyl alcohol as a granulating agent. Diclofenac sodium was used as a model drug. Tablet weight (250 mg) and diameter (9 mm) was kept constant. Tablets were evaluated for pharmacotechnical properties, drug content uniformity and in vitro drug release kinetics. Effect of gum concentration (10, 20 and 30% w/w with respect to total tablet weight) on in vitro drug release profile was examined. Both the gums produced matrix tablets with good strength and acceptable pharmacotechnical properties. Matrix tablets with 30% w/w gum copal and gum damar showed sustained drug delivery beyond 10 h. Drug release from gum copal matrix tablets followed zero order kinetics while gum damar (10 and 20% w/w) was found suitable to formulate the insoluble plastic matrix that releases the drug by diffusion. It is concluded that both gums possess substantial matrix forming property that could be used for sustained drug delivery.

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.

Evaluation of gum damar as a novel microencapsulating material for ibuprofen and diltiazem hydrochloride

A natural gum, damar was investigated as a novel microencapsulating material for sustained drug delivery. Microparticles were prepared by oil-in-oil emulsion solvent evaporation method. Ibuprofen and diltiazem hydrochloride were used as model drugs. Microparticles were evaluated for particle size, encapsulation efficiency and in vitro drug release kinetics. Images of the microparticles were obtained by bright field microscopy. The effect of different gum:drug ratios and solubility of drug on microparticle properties was principally investigated. Gum damar could produce discrete and spherical microparticles with both drugs. With a freely water soluble drug (diltiazem hydrochloride), gum damar produced bigger (45-50 µm) and fast drug releasing microparticles with low encapsulation efficiencies (44-57%). Contrary, with a slightly water soluble drug (ibuprofen), gum damar produced small (24-33 µm) microparticles with better drug encapsulation (85-91%) and sustained drug delivery. The increase in gum:drug ratio showed an increase in particle size, encapsulation efficiency and decrease in drug release rate in all cases. Drug release profiles of all microparticles followed zero order kinetics. In conclusion, gum damar can be used successfully to produce discrete and spherical microparticles of ibuprofen and diltiazem hydrochloride.

PEGylated rosin derivatives: Novel microencapsulating materials for sustained drug delivery

The aim of this study was to investigate PEGylated rosin derivatives (PRDs) as microencapsulating materials for sustained drug delivery. PRDs (D1, D2, and D3) composed of a constant weight of rosin and varied amounts of polyethylene glycol (PEG) 400 and maleic anhydride were synthesized in the laboratory. Microparticles were prepared by the O/O solvent evaporation technique using the acetone/paraffin system. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. The effect of the type of PRD, drug, PRD:drug ratio, viscosity of external phase, stirring speed, concentration of magnesium stearate (droplet stabilizer), and method of preparation on particle size, drug loading, and drug release profiles of microparticles was investigated. PRDs could produce discrete and spherical microspheres (with DFS) and microcapsules (with DLTZ). The drug loading value for microparticles was found to be in the range of 37.21% to 87.90%. The microparticle size range was 14 to 36 μm. The particle size and drug loadings of microparticles were substantially affected by the concentration of magnesium stearate and the type of drug, respectively. Most of the formulations could sustain the DFS and DLTZ release for 20 hours. DFS and DLTZ release from PRD microparticles followed Hixson-Crowell and first-order kinetics, respectively. The results suggest that PRDs can be used successfully to prepare discrete and spherical microparticles with DFS and DLTZ for sustained drug delivery.

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.

Sustained Release Microspheres of Diclofenac Sodium Using PEGylated Rosin Derivatives

The PEGylated derivatives of rosin-PD-1 and PD-2 synthesized and characterized earlier () were investigated as potential materials for sustained release microsphere prepared by emulsion solvent evaporation method using diclofenac sodium (DCS) as model drug. All the microspheres exhibited smooth surfaces intercepted by pores; their sizes (d90) ranged between 11–24 μm. The entrapment efficiency (< 80%) of the microspheres increased proportionally with derivative concentration. Presence of solvent like isopropyl alcohol or dichloromethane rendered the microspheres with large sizes but with reduced drug entrapment. Microspheres with small size were obtained at an optimum viscosity of liquid paraffin; any change lead to increase in the particle size. Magnesium stearate was found to be most suitable detackifier in the present system. The drug release was directly related to the particle size—small sized microspheres released drug at a faster rate. The dissolution data complied with Higuchi equation while the mechanism of drug release was Fickian diffusion (n ∼ 0.5). Controlled inhibition of edema, as tested by hind paw edema method, was observed for 10 h when the microspheres were administered intraperitoneally. The present study found the derivatives as promising materials for preparing microspheres for sustained delivery of DCS.

A comparative study of aqueous and organic-based films and coatings of PEGylated rosin derivative.

Rosin was partially esterified with polyethylene glycol 400 and reacted with maleic-anhydride to form an ester-adduct derivative. Derivative and native rosin were characterized for physicochemical properties. Aqueous coating system of derivative was developed by ammonia neutralization method. Organic-based films were produced using acetone. Aqueous and organic-based films were comparatively evaluated. Derivative exhibited an excellent coat-forming ability on spherical-units. Aqueous-based film exhibited very high water vapor transmission rate, wettability, water uptake, and leaching at pH 6.8. A 20% w/w aqueous-based coat could sustain diclofenac sodium release for 8 h, whereas, 20% w/w organic-based coat released 20.11% of drug in 8 h. In conclusion, aqueous coating system of synthesized rosin derivative can be developed; however, aqueous-coats are less efficient to retard the drug release rate. Instead, the organic-based coatings can efficiently be used for sustained drug delivery.

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.

Wound healing and antiinflammatory potential of madhu ghrita

Madhu ghrita is a herbal formulation containing honey and ghee (clarified butterfat) as its constituents. The aim of present study is to verify the wound healing and antiinflammatory claims of Madhu ghrita. Incision and excision wound models were used for evaluation of wound healing activity followed by histopathological study in which healing markers like keratinization, epithelization, fibrosis, neovascularisation and collagenation were evaluated in male Wistar rats. The results of Madhu ghrita were compared with the results of untreated control group and results of framycetine sulphate cream, considered as a positive control. The formulation was also tested for antiinflammatory activity, using carrageenan-induced paw oedema in male Wistar rats. The test formulation Madhu ghrita enhanced the tensile strength, which significantly improved over untreated wounds. The tensile strength of untreated control wound was 281±5.82, while with the Madhu ghrita and framycetine sulphate cream 1% w/w, it was 328±8.9 and 398±6.32, respectively. Treatment with Madhu ghrita alone promoted wound contraction and reduced the wound closure time, so increase in tensile strength and wound contraction shows the wound healing potential of Madhu ghrita . Histopathological study shows that proliferation of epithelial tissue promotes angiogenesis, multiplication of fibrous connective tissue due to treatment with Madhu ghrita . The test formulation Madhu ghrita also shows significant antiinflammatory activity when the results are compared with the activity of ibuprofen gel as reference standard. The present study demonstrates the wound healing and antiinflammatory potential of Madhu ghrita .

Study of biodegradation and biocompatibility of PEGylated rosin derivatives

PEGylated rosin derivatives are improved in series ester-adduct derivatives of rosin. The aim of this study was to assess biodegradation and biocompatibility of PEGylated rosin derivatives. Study employed two different PEGylated rosin derivatives, namely, D1 and D2, with constant weight of rosin and increasing amounts of polyethylene glycol 400. PEGylated rosin derivatives were synthesized and tailored into spherical beads and disks with smooth surface for use. In vitro degradation was studied at pH 4.0, 7.4, and 10 for 60 days. In vivo study was performed in Wistar rats using poly(d,l-lactide-co-glycolide) (50:50) as a control. Post 3, 7, 14, and 21 days of implantation, PEGylated rosin derivatives disks were retrieved and evaluated for weight loss, molecular weight decline, morphology, and tissue response. D1 and D2 beads showed 21.68% and 32.37% weight loss, respectively, at pH 7.4 post 60 days. Degradation was increased substantially with increase in pH of medium. Degradation of disks was markedly slower than that of beads. In vivo degradation of PEGylated rosin derivative disks was faster than in vitro. Post 60 days of implantation, weight loss of D1 and D2 disk was 7.57% and 11.84%, whereas molecular weight was declined by about 19% and 26%, respectively. Owing to higher amounts of polyethylene glycol 400, in vitro and in vivo degradation of D2 was faster than D1. Poly(d,l-lactide-co-glycolide) as well as PEGylated rosin derivative implants evoked mild inflammatory responses characterized by few macrophages and absence of exudation at tissue–disk interface. The cellular density in tissue surrounding PEGylated rosin derivative disks increased initially with time up to 7 days and decreased eventually at the end of 21 days. The trend was similar for poly(d,l-lactide-co-glycolide) implants. Increase in polyethylene glycol 400 improved biodegradation and biocompatibility of PEGylated rosin derivatives. Results revealed that PEGylated rosin derivatives degrade slowly in vivo over a period of time, possess fair biocompatibility, and thus are promising biomaterial for drug delivery applications.