Study of Novel Rosin-Based Biomaterials for Pharmaceutical Coating

Study of Novel Rosin-Based Biomaterials for Pharmaceutical Coating
Submitted: September 9, 2002; Accepted: October 14, 2002
Suniket V Fulzele1, Prashant M Satturwar1 and Avanash K Dorle1
1Department of Pharmaceutical Sciences, Nagpur University Campus, Amravati Road, Nagpur 440010, India



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 Young’s modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young’s 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 pel-lets 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 plasticiza-tion 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.


rosin, film coating, biomaterials, pellets, mechanical properties.


Rosin is a solid resinous mass obtained naturally in the oleoresin of pine trees. Principally it is composed of resin acids (abietic and pimaric) and a small amount of nonacidic components. Rosin and rosin derivatives are widely used in paints, varnishes, printing inks, chewing gums, and cosmetics. Pharmaceutically, rosin and its derivatives have been extensively studied. Rosin and rosin esters are reported as coating [1] and microencap-sulating [2,3] agents for sustained and controlled drug release. Esters of rosin have been used as hydrophobic matrix material in tablet formulation [4]. Derivatives of abietic acid, the principal component of rosin, have been investigated for drug delivery applications [5,6]. Re-cently, a few rosin-based polymers have been evaluated for their film forming and coating properties [7,8]. Rosin-glycerol ester is biodegradable, both in vitro as well as in vivo [9]. This study investigates the drug delivery appli-cation of 2 new rosin-based biomaterials. The biomate-rials are characterized and evaluated for their film form-ing and coating properties. Diclofenac sodium was selected as a model drug to evaluate the possible appli-cation of the 2 biomaterials to produce sustained-release coated forms.



Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were received as gift sam-ples from Derives Resiniques Terpeniques Inc, Gam-betta, France. Dibutyl sebacate (DBS) was obtained from Morflex Inc, Greensboro, NC. Diclofenac sodium was a gift sample from Zim Laboratories, Nagpur, India, and was used as received. Other reagents and chemi-cals were of analytical or Indian pharmacopoeial grade.

Material characterization

The biomaterials GMR and PMR were evaluated for the preliminary physicochemical properties such as color, acid value, softening point, and relative solubility using methods previously described [10]. For determination of the solubility, 2 g of material with 50 mL of solvent was placed in an airtight screw-capped tube and agitated for 24 hours at 25°C. Two mL of supernatant was withdrawn in a tared dish. Solvent was evaporated by a mild heat and the tared dish was weighed again. The difference in weight gives the amount of material dissolved in the sol-vent. Different solvents and pH solutions were used for this purpose, and the experiment was repeated 5 times for each solvent/buffer solution. Buffers of different pH were prepared by the method described in Indian Phar-macopoeia [11].

The molecular weight was estimated using a gel per-meation chromatography system (Perkin Elmer, series-10, Newton Center, Wellesley, MA) equipped with an Refractive index (RI) detector (La Chrom Detector L-7490) (Perkin Elmer). Samples were eluted through a PL gel 3 μ mixed column at a flow rate of 1 mL/min using tetrahydrofuran as a solvent. Polystyrene standards (Polysciences, Warrington, PA) were used for calibra-tion. The glass transition temperature (Tg) of GMR and PMR was determined by differential scanning calo-rimetry (DSC-Shimadzu, METTLER, TA4000, London, England). Approximately 15 mg of GMR and 10 mg of PMR samples were placed in an aluminium pan and scanned over a temperature range of 25°C to 250°C at the rate of 10°C/min. Scanning was performed in tripli-cate.

Film preparation and characterization

Films were cast from a dichloromethane solution con-taining 30% (wt/vol) film forming agent, on a mercury substrate employing the principle of solvent evaporation. Plasticizer dibutyl sebacate (DBS) was added at concen-trations of 0%, 10%, and 20% (wt/wt of the total solids) in the casting solution. Films were carefully cast on a 20-cm-diameter petri dish containing mercury (area of cast-ing: 19.5 cm2). After allowing the solvent to evaporate for 24 hours, the films were removed from the plate without difficulty and subsequently air dried for an additional 24 hours. The prepared films were carefully cut into strips (approximate dry film thickness: 0.4 mm; 12 mm width x 120 mm length), and the mechanical properties of the films were evaluated using Instron instrument (model 4467, Instron Corp, Canton, MA). The tests were con-ducted at 23 ± 1°C and 50% relative humidity employing a gauge length of 50 mm and cross head speed (CHS) of 5 mm/min. The stress-strain parameters including the tensile strength, percentage elongation at break, and Young’s modulus were determined for each film speci-men with at least 3 repetitions. The films were further characterized in terms of water vapor transmission rates (WVTR) and moisture absorption employing the meth-ods described previously [8]. The studies were con-ducted by employing controlled relative humidities (RH) of 23%, 43%, 75%, and 93% achieved by using different saturated salt solutions containing excess solute.

Preparation of coated pellets

Drug model, diclofenac sodium, was initially layered onto 14/16-mesh nonpareil seeds (NPS) using a conventional coating pan (Retina India Company, Mumbai, India). For a 50-g batch size, 6 g of drug and 0.3 g povidone were dissolved in 50 mL of 95% ethanol to prepare the drug-binder solution, which was then sprayed over the cas-cading NPS by solution-layering technique [12]. After drying at 50°C, the drug-layered pellets were succes-sively coated with F3 and F6 formulations of film coating solutions until different levels of coat consumption (per-centage weight increase) were reached. The coating ex-periments were performed under conditions of inlet air temperature 70°C to 75°C, pellet bed temperature 40°C to 45°C, spray rate 1 mL/min, spray gun position 15 cm from pellet bed surface, and atomizing pressure 40 psi. The coated pellets were transferred and air dried at room temperature.

Intact pellets and cross-sectioned pellets were studied under a scanning electron microscope (Stereo Scan 250-MK-III, Cambridge, England). Samples were mounted on stubs and gold coated for 120 seconds us-ing a sputter coater (Jeol JXA-840 A, London, England) under an argon atmosphere before examination under the scanning electron microscope.

Drug release analysis

Analysis of drug release from coated pellets was fol-lowed in 900 mL of 0.1 N HCl (pH 1.2) for first 2 hours followed by 900 mL of phosphate buffer solution (pH 6.8) up to 10 hours. The test was conducted using US Phar-macopeia XXIII dissolution apparatus 2 (Veego Scien-tific, Mumbai, India) at 37 ± 1°C at a speed of 100 rpm. Aliquots were withdrawn at specific predetermined time intervals and exchanged with new media of the same volume maintained at the same temperature. The amount of drug released was estimated spectropho-tometrically at 276 nm with triplicate measurements.


Preliminary characterization of GMR and PMR is shown in Table 1. Esterification of rosin acids is evident from the acid values of the biomaterials, which are signifi-cantly reduced compared with rosin (155 mg of KOH). Absence of a sharp melting point indicates the amor-phous nature of the biomaterials. The molecular weights for GMR and PMR are 1860 and 2700, respectively, with polydispersity index close to 1. The Tg was determined using a differential scanning calorimeter with the pentae-rythritol ester showing higher value compared with glyc-erol ester. The relative solubility showed low solubility of both the biomaterials in water (Table 2). They are freely soluble in almost all organic solvents. A pH-dependent solubility is observed with both the biomaterials showing increased solubility in alkaline medium.

Table 1. Characterization of Biomaterials*
Parameters GMR PMR
Color Light brown Light brown
Acid value (mg of KOH) 40.0 29.6
Softening point (°C) 85~90 110~115
Molecular weight (Mw) 1860 2700
Polydispersity (Mw/Mn) 1.12 1.03
Tg (°C) 72.8 91.4
*GMR indicates glycerol ester of maleic rosin; PMR, pentaerythritol ester of maleic rosin; Tg, glass transition temperature; Mw, weight average molecular weight; Mn, number average molecular weigh.


Table 2. Relative Solubility of Biomaterials

Film characterization

Various film formulations given in Table 3 were used for preparation of films. This study examines the effect of plasticizer on the mechanical, WVT, and moisture-absorption properties of GMR and PMR films. The plas-ticized and nonplasticized films were prepared by solvent evaporation/casting technique. Films produced from the plasticizer-free solutions were smooth and transparent but brittle. Improvement in the mechanical properties was attempted by addition of plasticizers. The addition of plasticizers plays a critical role in the per-formance of film coating [13], which results in decreased tensile strength, lowered Tg, and increased elongation and flexibility of the films [14]. In this study, the effect of plasticizer concentration was investigated by the addition of 10% and 20% wt/wt (based on polymer weight) of a hydrophobic plasticizer, dibutyl sebacate (DBS), to the film casting solutions. For both GMR and PMR, plasti-cizer level of 20% wt/wt was sufficient to obtain films that were flexible enough to be bent in the dried state without breaking. The mechanical properties of free films are generally defined by stress-strain data, which serve to characterize polymer properties [15]. The average re-sults of the mechanical property measurements are shown in Table 4.

Table 3. Formulations of Film Coating Solutions*
Ingredient Composition (% wt/vol)
F1 F2 F3 F4 F5 F6
GMR 30.0 30.0 30.0
PMR 30.0 30.0 30.0
DBS 3.0 6.0 3.0 6.0
Dichloromethane q.s. to 100.0 100.0 100.0 100.0 100.0 100.0
*GMR indicates glycerol ester of maleic rosin; PMR, pentaerythritol ester of maleic rosin; DBS, dibutyl sebacate; q.s., Quantity sufficient.


Table 4. Mechanical Properties of Free Films*
Film formulation F1 F2 F3 F4 F5 F6
Thickness (mm) 0.38 0.40 0.42 0.40 0.42 0.43
Tensile strength (Mpa) 0.32 0.37 0.39 0.41 0.47 0.49
Elongation (%) 7.12 17.26 30.41 10.42 18.07 24.10
Young’s modulus (MPa) 4.50 2.09 1.30 3.90 2.23 2.02

*Average of 4 determinations.

Incorporation of DBS up to 20% of polymer weight did not significantly affect the film thickness. Plasticized films show higher elongation (%), although the tensile strength is nearly constant. The low value for the tensile strength of all the films may be attributed to the low mo-lecular weight of the biomaterials. Young’s modulus is the constant of proportionality of stress to strain and is equal to the slope of the straight line portion of the stress-strain curve [16]. In the present study, the addition of DBS decreased the value of Young’s modulus, which may contribute to an increase in the adhesion between the film and coating surface [17]. Although the tensile strength values suggest the risk of film cracking, no sign of cracking in either the free films or coated forms was observed, which may partly be attributed to the lower values of Young’s modulus. Elongation is defined as the measure of the capacity of a film to deform prior to fail-ure [18]. Lower elongation indicates a low deformation capacity of the film and a brittle film structure. DBS in-creased the percentage elongation of GMR and PMR films suggesting the suitability of adding DBS, which may increase the film flexibility and reduce the brittle state. These results can be attributed to an increase in the elasticity of the polymer and a lowering of the inter-nal stresses within the film.

The results of the WVTR study are shown in Table 5. The low rates of water vapor transmission exhibited bythe film formulations are in accordance with the hy-drophobic nature of the biomaterials as demonstrated by their extremely low solubility in water. The transmission-rates were further decreased by addition of plasticizer, which may be due to better film formation with the addi-tion of dibutyl sebacate. A clear correlation was ob-served between the water vapor permeability and plasti-cizer concentration. The film formulations may therefore promise considerable utility in providing protection to the coated forms against moisture. This expectation is fur-ther supported by the results of the moisture absorption study shown in Table 6. Plasticized films of DMR and PMR show a drop in the percentage of moisture ab-sorbed when compared with free films. Even at 93% RH, the films absorb only 1% to 2% moisture, which is indica-tive of their hydrophobic and moisture-resistant proper-ties.

Table 5. WVTR Study of Free Films*
Film Formulations Thickness (cm) Area (cm2) WVTR† (g.cm/cm2/24 h) x 10−5 at RH
43% 93%
F1 0.037 4.34 1.75 ± 0.06 4.68±0.15
F2 0.040 4.32  1.29±0.08 4.08±0.12
F3 0.042 4.34 0.96±0.07 3.60±0.18
F4 0.039 4.32 4.25±0.18 6.72±0.20
F5 0.041 4.34 3.42±0.10 5.77±0.16
F6 0.044 4.34 2.87±0.09 5.04±0.14

*WVTR indicates water vapor transmission rates; RH, relative humidities.
†Each value is mean ± SD of 4 determinations.


Table 6. Moisture Absorption Study of Free Films*
Film Formulation Percent Moisture Absorbed at RH†
23% 43% 75% 93%
F1 0.13 0.30 0.66 1.00
F2 0.10 0.20 0.59 0.92
F3 0.08 0.23 0.56 0.87
F4 0.21 0.41 0.66 1.20
F5 0.17 0.36 0.61 1.11
F6 0.13 0.34 0.57 1.07
*Average of 3 determinations.
†RH indicates relative humidities.


Pellet coating

Coating experiments performed using film solutions F1 and F4 posed a few problems such as sticking of coated forms with the pan surface being associated with film cracking and increased time required to obtain desirable level of coat build-up. Both these problems were effec-tively overcomed by using plasticizer-containing film coating solutions. The representative scanning electron micrographs of pellets coated with film formulation F3 and F6 is shown in Figure 1 and Figure 2, respectively. The coated pellets are round shaped with a fairly smoothsurface. The cross-section shows distinct layers of core (NPS), drug layer, and coat. The core appears grained, while the coat displays a smooth surface with the drug layer compacted in between. No sign of crack-ing was observed on the surface as indicated by the smooth and uniform coat layer.

The release of DS from coated pellets depends on the percentage of the film-coat layer. The results from disso-lution tests show that increasing the coating level de-creased the drug release from coated pellets, which suggests that the film coat may be controlling the re-lease process. The diffusion of the drug through a thicker membrane seems to govern the release profile. The results for film-coating solutions F3 and F6 are shown in Figure 3 and Figure 4, respectively. Use of plasticizer was found to be imperative in performing coating experiments within reasonable time and process conditions. Nearly 20% of the drug was released for first 2 hours (pH 1.2), which may be due to poor solubility of drug in acidic medium [19] or the acid-resistant nature of biomaterials.

Figure 1. Representative scanning electron micrographs of pellets coated with formulation F3 (a) coated pellet (b) cross-section of coated pellet (c) surface of coated pellet.

Figure 2. Representative scanning electron micrographs of pellets coated with formulation F6 (a) coated pellet (b) cross-section of coated pellet (c) surface of coated pellet.Figure 3,4 In vitro drug release from pellets coated with film formulation


Two rosin-based biomaterials, GMR and PMR, investi-gated in this study showed good film-forming and -coating properties. Addition of plasticizer (DBS) im-proved the film characteristics by increasing the flexibility associated with increase in elongation and decrease in Young’s modulus. All the film formulations show low rate of WVT and extremely low percentage of moisture absorption, promising the utility of the biomaterials in moisture-resistant dosage forms. The film characteriza-tion studies showed DBS to be an effective and com-patible plasticizer for both biomaterials. Coating experi-ments were conveniently performed using plasticizer-containing film formulations, with sustained drug release for up to 10 hours with increase in coat build-up.


The authors express their sincere gratitude to Viswesh-warya Regional College of Engineering (V.R.C.E.), Nag-pur, India, for the Instron facility and to Dr S.G. Wadod-kar, Head, University Department of PharmaceuticalSciences (U.D.P.S.) Nagpur, India, for providing the facilities.


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