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Volume 2013 Supplement, Issue 5
The authors describe the background and applications of fully formulated aqueous shellac for film-coating systems.
Shellac is a polymer used in coating applications to provide various functional properties. It can be used in film coatings to achieve enteric applications, aesthetic and immediate- release properties, taste masking, and seal coating. The authors describe the background and applications of fully formulated aqueous shellac for film-coating systems.
Shellac is a natural and versatile polymer used for coating applications. It is is used in the pharmaceutical and nutraceutical industries to provide various functional properties. It can be used in film coatings to achieve enteric applications, aesthetic and immediate-release properties, taste masking, and seal coating. It is recognized by the National Formulary (NF) and is classified into categories as orange, de-waxed orange, bleached, and refined de-waxed bleached. Shellac is an approved food additive in the United States and in Europe and is also listed in the United States Pharmacopeia, European Pharmacopoeia, Japanese Pharmacopoeia, Food Chemicals Codex, and in the European food regulations as E904. It also has generally recognized as safe (GRAS) status as designated by FDA.
Shellac is a resin derived from insects, the Kerria Lacca species (family name Coccidae), also known as lac, which are cultivated in India, Thailand, China, and Vietnam. Shellac is produced from the lac insect’s resinous secretion, which occurs when lac insects attach themselves to the bark of particular host trees and feed on the tree’s sap. The lac insect’s resinous secretion forms in cocoon-like masses on the trees and branches. The cocoon-like masses are physically removed from the host trees. The secretion material harvested is called sticklac, and two crops per year are cultivated or harvested. The sticklac is washed with an aqueous media to remove excess laccaic acid, a red dye, and is filtered and dried. The dried resin is called seedlac because of its seed-like resemblance (1). Seedlac purity is approximately 85-90%, consisting of 5-8% shellac wax and 2-5% impurities. To refine shellac for pharmaceutical use, the seedlac is further processed to the de-waxed grade to increase the purity to the specifications set forth by the NF (2).
Shellac structurally consists of esters from polyhydroxy carboxylic acids and other polar and nonpolar components within the molecule. The four main carboxylic acid components are: aleuritic (35%), jalaric (25%), shellolic (8%), and butolic (8%). Typically, enteric coatings consist of polymers with acidic functional groups. The acid groups are protonated in an acidic environment making the shellac water-insoluble in the stomach.
Esterification can be inhibited when using certain plasticizers. A combination of plasticizers and surfactants improves shellac’s flexibility and increases the adhesive structural reinforcement properties of the film. Shellac formulations (e.g., Protect EN, Sensient) have proven successful in functional reproducibility and product stability over time. With the addition of sodium alginate, the enteric film-coating system provides gastric protection with good film adhesion and flexibility for particles, tablets, and capsules.
Shellac can be used to produce films with targeted functionality to meet desired dosage release within the physiological pH ranges of the digestive tract. Table I depicts the pH range of various anatomical regions.
Table I: Annatomical pH.
~5.6 to 7.9
~ < 60 s
~6.5 to 7.0
~10 to 15 s
~1 to 1.2
(fed state: ~4)
~ 80.5 to 120 min
(half emptied: 80.5 min)
~ 1.5 to 5 h
Variable pH--Bowel evacuation dependency
As seen in Table I, it may be desirable to have coating systems that are designed to release at various pH ranges for targeted drug delivery. However, variability in the pH ranges exists due to the stomach’s physiology and is subject to multiple factors, including age, illnesses, medications taken, and food intake (i.e., fed state). In a fed state, the stomach acidity can rise to a pH of 4, and the stomach empting may be delayed for two to four hours. In a fasted state, gastric empting could occur rapidly in less than one hour. Many pharmaceutical and nutraceutical dosage forms must pass through the stomach before releasing in the lower gastrointestinal (GI) tract. Dosage release from an enteric coating is possible in the more pH-neutral region of the digestive tract due to shellac carboxylic acid deprotonation that allows the shellac to become more water-soluble.
Researchers at the Institute of Pharmacy at Leipzig in Germany coated substrates using an aqueous shellac formulation in combination with various polymers: polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and carbomer 940, a cross-linked polyacrylic acid polymer (3). This study was designed to understand the effect of enteric properties using different polymers with shellac. The testing results showed cracking of the PVA/shellac films and water was allowed to enter the core. HPMC/shellac film data indicated pore formation resulting in premature drug release. Carbomer 940 resulted in a swelled film leading to increased drug release through the shellac coating. The hydrophilic polymers, PVA and HPMC, used in the study showed variability in disintegration profiles over 3, 6, and 12 months. When shellac was used in combination with sodium alginate, the dissolution stability was maintained both in real time and accelerated studies (3).
The data used in Figures 1 and 2 are from the combination of shellac (Protect EN) and sodium alginate. The stability study was performed at room temperature, H2 (25 °C/60% RH), and H4 (40 °C/75% relative humidity [RH]) conditions. Disintegration testing followed USP 35-NF30. Figure 1 indicates passing disintegration results after six months in an accelerated stability study.
Figure 2 indicates that enteric and seal-coating functionality and stability on ibuprofen release in a strongly acidic environment of the stomach with a weight gain of 3%.
The orange line in Figure 2 indicates no release of the Ibuprofen in simulated gastric fluid (SGF), which is characteristic of a true enteric coating where no breaching occurs in the stomach region. The red line in Figure 2 indicates some release when shellac was used without sodium alginate, making the shellac only coating a seal coat but not an enteric coat. Sodium alginate must be present to maintain the enteric properties of the system.
Shellac has vapor-barrier properties that prevent moisture from migrating into and out of a coated substrate. Shellac can act as a particle or core stabilizer and coats easily, providing a strong, hard and adhesive functional film. The adhesive property of shellac is due to the structural orientation of polar groups onto smooth surfaces (4). When shellac is coated onto a surface, the shellac must be applied in thin layers (low-weight gains) to promote efficiently dried film coats. Shellac has a thermal plasticity property that creates soft films when heated and harder films when cooled. This thermal plasticity property of shellac in part is due to the low transition glass temperatures (Tg) of shellac. The typical Tg of shellac ranges between 3749°C (5). The Tg range of shellac is correlated to the acid value content of shellac. The decrease in shellac’s acid value has an increasing effect on the Tg. Strong functional films, therefore, can be formed when coating at low temperatures while achieving desired functional properties. Coating at low temperatures is beneficial when either substrates or cores are sensitive to heat.
To test the barrier properties of shellac, shellac (Protect EN, Sensient) was applied to arginine base cores at 1, 2, 3, 4, and 5% weight gains using 2428% solution solids (Protect EN, Sensient) and a coating-bed temperature of 32-35°C. Moisture vapor sorption was measured using a thermal gravimetric analyzer (Perkin Elmer). The results in Figure 3 show that shellac applied at a 0.5 to 2% weight gain provides the necessary protection against moisture sorption.
The resulting parabolic curve in Figure 3 identifies the actual absorption of water in shellac films at different weight gains. A thin film is adequate to establish a good moisture barrier. The low weight gain confirms the functional property of shellac providing hard, resistant film properties. Counterintuitively, thicker films of shellac result in water retention as indicated by the parabolic curve in Figure 3.
Figure 3: Permeation results for shellac.
Shellac has two resinous fractions: hard, or pure, resin and a soft resin (6). The hard resinous fraction of shellac constitutes 70% of shellac’s structure. The hard resin is derived from four aleuritic acid units (6). The soft resinous fraction of shellac is derived from the erythrolaccin component. The orange/red color of shellac comes from primarily erythrolaccin, which is soft and sticky. The chemical properties of erythrolaccin are a mixture of various hydroxylated fatty acids and esters, including jalaric acid esters. Controlling the amount of residual erythrolaccin in the shellac may be a crucial part of the shellac purification. Using bleached shellac may provide a solution to overcoming stickiness in shellac films. It is hypothesized that hydrogen bonding between the water and shellac’s free hydroxyl groups, from the erythrolaccin, can create coating problems due to water retention in the film. Slightly tacky films could develop due to excess moisture in the films. When films are completely dry, the shellac film becomes resistant to moisture.
Figure 4: Shellac as a taste-maskant. WT is weight.
To investigate other functional properties of shellac, a test was performed to determine if shellac could be used as a taste maskant. A bitter drug (ibuprofen) was coated to a 3% weight gain. The coated and uncoated ibuprofen tablets were subjected to dissolution testing at a pH of 5.5 and 6.8. The pH range of 5.5 and 6.8 was used in alignment with the International Journal of Drug Testing (7) data on the normal pH range of the mouth. This pH range is influenced by patient age. Children have a higher oral cavity pH, and adult oral cavity pH varies with an average of 6.7. The test time period was 60 s, which correlates to the approximate time drug substances are held in the mouth prior to ingestion/swallowing. Timed sample intervals were pulled from the dissolution apparatus and drug-release data were collected using UV-visible absorbance measurements. A UV-visible spectrophotometer (Lambda 35 UV WinLab V6.0, Perkin Elmer) was used with variable (0.5, 1.0, 2.0, and 4.0 nm) bandwidths with wavelength ranges from 190 to 1100nm having scanning speeds of up to 2880nm/min with quartz-coated optics. Figure 4 depicts the dissolution response of ibuprofen release at a pH of 5.5 and 6.8. The response shows when ibuprofen is coated to 3% weight gain, there is no ibuprofen released at a pH of 5.5 to 6.8, thereby suggesting shellac to be a taste-masking functional coating.
Researchers at the Berlin College of Pharmacy supports the suggested versatility of shellac and have found shellac to have functions as a film former (8). According to Pearnchob et al., shellac-coated tablets showed moisture protection and taste-masking effects (8). Shellac also proved to increase the stability of acetaminophen compared with HPMC-coated systems, irrespective of the storage humidity. Pearnchob et al. found shellac coatings to effectively mask the unpleasant taste of acetaminophen tablets. Ammoniated aqueous shellac was also found to be an effective binder in wet granulations for extended release in compressed matrix tablets.
Shellac, either in enteric or seal coating forms, can provide new opportunities for functionally diverse coating systems. Shellac based on aqueous ammoniated and plasticized coating products can expand the functionality and stability attributes beyond what is available with other systems. Shellac provides a naturally derived, versatile polymer choice to the pharmaceutical and nutraceutical industries for product function and protection.
1. Y. Farag and C.S. Leopold, University of Hamburg, Institute of Pharmacy, Department of Pharmaceutical Technology, Bundesstrasse 45, 20146 Hamburg, Germany.
2. USP, USP36-NF31 Page 2192 (Rockville, Md, 2013).
3. B. Qussi and WG Suess, Drug DEV Ind Pharm, 31(1): 99-108 (2005).
4. S.K. Sharma, S. K. Shukla , and D. N. Vaid, Delhi Def Sci J. 33 (3), 261-271 (1983).
5. Y. Farag and C.S. Leopold, Diss. Techn., May: 33-39 (2009).
6. A. Tschirch and A. Farner, Arch. Pharm., 237 (1989).
7. Karin M. Höld et al., Intern. Journal of Drug Testing.
8. N. Peamchob, J. Siepmann, and R. Bodmeier, “Pharmaceutical applications of shellac: moisture-protective and taste-masking coatings and extended-release matrix tablets,” PubMed.gov, accessed Aug. 9, 2013.
About the Authors
Beverly Schad* is a technical support manager, Houston Smith is a technical director, Brian Cheng is a formulation scientist, Jeff Scholten is a chemist, Eric VanNess is a technical support manager, and Tom Riley is a formulations manager, all at Sensient Technologies; email@example.com.
*To whom all correspondence should be addressed.