Functional Category
Tablet and capsule diluent; tablet and capsule disintegrant; tablet binder; thickening agent.
Applications in Pharmaceutical Formulation
Starch is a versatile excipient used primarily in oral solid-dosage formulations where it is utilized as a binder, diluent, and disintegrant. As a diluent, starch is used for the preparation of standardized triturates of colorants, potent drugs, and herbal extracts, facilitating subsequent mixing or blending processes in manufacturing operations. Starch is also used in dry-filled capsule formulations for volume adjustment of the fill matrix,(1) and to improve powder flow, especially when using dried starches. Starch quantities of 3–10% w/w can act as an antiadherent and lubricant in tableting and capsule filling. In tablet formulations, freshly prepared starch paste is used at a concentration of 3–20% w/w (usually 5–10%, depending on the starch type) as a binder for wet granulation. The required binder ratio should be determined by optimization studies, using parameters such as tablet friability and hardness, disintegration time, and drug dissolution rate. Starch is one of the most commonly used tablet disintegrants at concentrations of 3–25% w/w;(2–7) a typical concentration is 15%. When using starch, a prior granulation step is required in most cases to avoid problems with insufficient flow and segregation. A starch– lactose compound has been introduced enabling the use of granular starch in direct compression, improving the tableting process and the disintegration time of the tablets.(8,9) However, starch that is not pregelatinized does not compress well and tends to increase tablet friability and capping if used in high concentrations;(10) see also Table I. Balancing the elastic properties of starch with adapted excipients has been shown to improve the compaction properties in tableting.(8,11) Starch, particularly the fine powders of rice and wheat starch, is also used in topical preparations for its absorbency of liquids. Starch paste is used in ointment formulations, usually in the presence of higher ratios of glycerin. Starch has been investigated as an excipient in novel drug delivery systems for nasal,(12) and other site-specific delivery systems.(13,14) The retrogradation of starch can be used to modify the surface properties of drug particles.(15) Starches are useful carriers for amorphous drug preparations, such as pellets with immediate or delayed drug release obtained, for example, by melt extrusion,(16,17) and they can improve the bioavailability of poorly soluble drugs. Starch, particularly rice starch, has also been used in the treatment of children’s diarrheal diseases. Specific starch varieties with a high amylose content (resistant starches) are used as insoluble fiber in clinical nutrition, and also for colon-targeting applications.(18) Due to their very high gelatinization temperature, these starches are used in extrusion/spheronization processes.(19) Starches with a high amylopectin content (waxy starches) are used as the starting material for the synthesis of hydroxyethyl starch, a plasma volume expander. Native starches conforming to pharmacopeial specifications are used as the raw materials for the production of starch-based excipients and active pharmaceutical ingredients, frequently covered with their own pharmacopeial monographs
Description
Starch occurs as an odorless and tasteless, fine, white to off-white powder. It consists of very small spherical or ovoid granules or grains whose size and shape are characteristic for each botanical variety.
Stability and Storage Conditions
Dry starch is stable if protected from high humidity. Starch is considered to be chemically and microbiologically inert under normal storage conditions. Starch solutions or pastes are physically unstable and are readily metabolized by microorganisms; they should therefore be freshly prepared when used for wet granulation. Starch should be stored in an airtight container in a cool, dry place.
Incompatibilities
Starch is incompatible with strongly oxidizing substances. Colored inclusion compounds are formed with iodine.
Safety
Starch is an edible food substance, considered a food ingredient and not a food additive. It is regarded as an essentially nontoxic and nonirritant material.(25) Starch is therefore widely used as an excipient in pharmaceutical formulations. 5.0 0.0 − 10000 5.0 × [2nd deriv. log(1/R)] 1100 1300 1500 1700 1900 2100 2300 2500 Wavelength/nm −0.2 0.3 1201 log(1/R) 1434 1699 1929 2283 2322 2299 2398 2244 2015 1887 1391 Figure 4: Near-infrared spectrum of starch measured by reflectance. 5.0 0.0 −5.0 10000 × [2nd deriv. log(1/R)] 1100 1300 1500 1700 1900 2100 2300 2500 Wavelength/nm −0.2 0.5 1201 log(1/R) 1433 1394 1887 2012 2242 2300 2398 2323 2283 1927 Figure 5: Near-infrared spectrum of corn starch measured by reflectance. 3.0 0.0 10000 −4.0 × [2nd deriv. log(1/R) 0.2 1201 1434 1777 1929 2322 2282 2015 2244 2298 2399 1393 1887 log(1/R) −0.2 Wavelength/nm 1100 1300 1500 1700 1900 2100 2300 2500 Figure 6: Near-infrared spectrum of rice starch measured by reflectance. 5.0 0.0 10000 −5.0 × [2nd deriv. log(1/R) 0.4 1434 1699 1929 2322 2283 2014 2242 2299 2398 1391 1887 log(1/R) −0.2 Wavelength/nm 1100 1300 1500 1700 1900 2100 2300 2500 Figure 7: Near-infrared spectrum of wheat starch measured by reflectance. Particle diameter (μm) Volume (%) Corn starch Pea starch Rice starch Potato starch Tapioca starch Wheat starch 0 1 2 3 4 5 6 7 8 9 10 11 12 13 0.04 0.06 0.1 0.2 0.4 0.6 1 2 4 6 8 10 20 40 60 100 200 400 600 1000 2000 Figure 8: Particle size distribution of commercial starches (laser method, volume distribution). S Starch 689 Both amylose and amylopectin have been evaluated as safe and without limitation for daily intake.(26) Allergic reactions to starch are extremely rare and individuals apparently allergic to one particular starch may not experience adverse effects with a starch from a different botanical source. The wheat proteins (gluten) are problematic for conditions such as celiac disease. Contamination of surgical wounds with the starch glove powder used by surgeons has resulted in the development of granulomatous lesions.(27) LD50 (mouse, IP): 6.6 g/kg(28)