Name: Starch
CAS No: Starch [9005-25-8]
BP: Maize starch Potato starch Rice Starch Tapioca Starch Wheat Starch JP: Corn Starch Potato Starch Rice Starch Wheat Starch PhEur: Maize Starch Pea Starch Potato Starch Rice Starch Wheat Starch USP-NF: Corn Starch Potato Starch Tapioca Starch Wheat Starch
Amido; amidon; amilo; amylum; C*PharmGel; Eurylon; fecule; Hylon; maydis amylum; Melojel; Meritena; oryzae amylum; Pearl; Perfectamyl; pisi amylum; Pure-Dent; Purity 21; Purity 826; solani amylum; tritici amylum; Uni-Pure.
Starch [9005-25-8]
(C6H10O5)n where n = 300–1000. Starch consists of linear amylose and branched amylopectin, two polysaccharides based on a-(D)-glucose. Both polymers are organized in a semicrystalline structure, and in the starch granule, amylopectin forms the crystalline portion. The exact structure of starch is not yet fully understood. There is no specific distribution pattern of amylose and amylopectin molecules in the starch grain. Both molecules are organized in similar structures, probably as clusters according to the most recent scientifically recognized models. The different configurations of these molecules result in different behavior in cold aqueous solutions. Amylose (only linear 1,4 bonds) shows a high tendency for crystallization (retrogradation) resulting in insoluble adducts, whereas amylopectin (branched polymer) shows slow jellification, forming opaque and highly viscous preparations after some days. See also Sections 5 and 10. The molecular weight depends on the origin and the nature of the starch. It can range between 50 and 500 million Da, with amylopectin having a higher molecular weight than amylose.
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
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
See Table I.
Acidity/alkalinity Aqueous dispersions of starch usually have a pH in the range 4.0–8.0. Starch does not exhibit a significant self-buffering capacity. Amylose content 24–28% for corn starch; 35–39% for pea starch; 20–23% for potato starch; 17–20% for tapioca starch; 24–28% for wheat starch. Compactability see Figure 1. Density (bulk) (depending on the industrial process and humidity) 0.45–0.58 g/cm3 for corn starch;(20,30) 0.56–0.82 g/cm3 for potato starch;(20) 0.50 g/cm3 for wheat starch. Density (tapped) (depending on the industrial process and humidity) 0.69–0.77 g/cm3 for corn starch;(20) 0.80–0.90 g/cm3 for potato starch;(20) 0.76 g/cm3 for wheat starch. Density (true) 1.478 g/cm3 for corn starch. Flowability Commercial starch is generally cohesive and has poor flow characteristics. The flow properties depend strictly on the moisture content,(20,21) and drying can result in a free-flowing material. Gelatinization temperature (measured at 20% w/w in water with differential scanning colorimetry (peak)) 718C for corn starch; 628C for pea starch, 648C for potato starch; 688C for rice starch; 598C for wheat starch. Gelatinization causes the rupture of the starch grains and is an irreversible loss of the structure of the starch particle.(22) Moisture content All starches are hygroscopic and absorb atmospheric moisture to reach the equilibrium humidity.(23,24) The approximate equilibrium moisture is characteristic for each starch. At 50% relative humidity: 12% for corn starch; 14% for pea starch, 18% for potato starch; 14% for rice starch; 13% for wheat starch. Excessively dried starches with a humidity lower than the equilibrium humidity, are commercially available. These products should be stored in hermetically sealed containers to maintain their low moisture content. See also Figures 2 and 3. NIR spectra see Figures 4, 5, 6, and 7. Particle size distribution Corn starch: 2–32 mm; average particle diameter 13 mm; Pea starch: 5–90 mm; average particle diameter 30 mm; Potato starch: 10–100 mm; average particle diameter 46 mm; Rice starch: 2–20 mm; average particle diameter 5 mm; Tapioca starch: 5–35 mm; average particle diameter 13 mm; Wheat starch: 2–45 mm; bimodal particle size distribution, peak values approx. 2 mm and 20 mm Solubility Practically insoluble in cold ethanol (96%) and in cold water. Starch swells instantaneously in water by about 5–10% at 378C.(3) Starch becomes soluble in hot water at temperatures above the gelatinization temperature. Starches are partially soluble in dimethylsulfoxide and dimethylformamide. Specific surface area 0.40–0.54 m2 /g for corn starch.(8) Swelling temperature Swelling is a reversible process.(22) 648C for corn starch; 638C for potato starch; 728C for rice starch; 558C for wheat starch Viscosity (dynamic) Nonmodified starches are not the preferred polymer for regulating the viscosity of pharmaceutical preparations, except for clinical nutrition products. This is due to the physical and microbial instability of starch paste. In food applications, starch contributes to higher viscosity via the volume effect of the swollen particles and not with its dynamic viscosity. The viscosities of starch paste, obtained and measured under similar conditions may be ranked as follows: potato starch >> tapioca starch > corn starch. Note that aqueous starch dispersions show significant rheopexy, especially at concentrations above 40% w/w
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.
Starch is incompatible with strongly oxidizing substances. Colored inclusion compounds are formed with iodine.
Starch is extracted from plant sources with specific processes according to the botanical origin. Typical production steps are steeping (corn), wet milling (corn, potato), dry milling (wheat), or sieving and physical separation with hydrocyclones. The last production step is usually a centrifugal separation from the starch slurry followed by drying with hot air. The starch separation process may use sulfur dioxide or peroxides as a processing aid, improving the separation process and the microbial quality of the final product
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. 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)
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection and a dust mask are recommended. Excessive dust generation should be avoided to minimize the risks of explosion. The minimal explosive concentration of corn starch is 30–60 g/m3 air. In the UK, the long-term (8-hour TWA) workplace exposure limits for starch are 10 mg/m3 for total inhalable dust and 4 mg/m3 for respirable dust.(29
GRAS listed. Included in the FDA Inactive Ingredients Database (buccal tablets, oral capsules, powders, suspensions and tablets; topical preparations; and vaginal tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients
Dextrin; hydroxypropyl starch; maltodextrin; sodium starch glycolate; starch, pregelatinized; starch, sterilizable maize.
Note that corn starch is also known as maize starch and that tapioca starch is also known as cassava or manioc starch. Corn starch, potato starch, rice starch, and wheat starch have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. Starch is isolated from vegetable sources. Pure starch should only contain traces of foreign matter (e.g. tissue fragments) and no traces of starches other than from the declared botanical origin. Inside their crystalline structure, starch particles contain smaller quantities of lipids (0–0.8%) and proteins (0–0.5%). The contents are relatively stable and typical for each starch variety. Starches from different plant sources differ in their amylose/amylopectin ratio (see also Section 10). Differences in the physical properties of the various starches mean that they are not automatically interchangeable in a given pharmaceutical application. Corn starch is also available in a naturally white variety (extra white corn starch), containing low levels of carotenoids (especially lutein and zeaxanthin). This starch variety is extracted from specific and nongenetically modified organism hybrids of Zea mays L. Bleached starches are considered as modified (oxidized) starches. They are not interchangeable with nontreated starches for regulatory and technical reasons.(30) The pharmacopeial monographs for starch do not include an assay for starch content. Possible analytical methods for quantification are polarimetric(31) or enzymatic tests.(32) Modified starch and modified pregelatinized starch are listed in USP32–NF27. Waxy corn starch derivatives are used to increase the viscosity of liquid products such as syrups and nutritional preparations. Modified and pregelatinized starches are valuabl excipients in hydrophilic matrix systems for controlled drug release.(33,34) Gelatin-free hard and soft capsules and caplets are made in some cases with specific modified starches, especially the hydroxypropylated grades. Amphiphilic starch derivatives improve the solubility of drugs(35,36) and may be used to make microcapsules and nanoparticles. Hydrophobic starch derivatives serve as ingredients in creams and ointments to reduce the stickiness on the skin. Modified starches exhibit excellent film-forming properties and are therefore valuable excipients in the film-coating of tablets and capsules, and in the production of oral edible films.(37) Instant Pure-Cote, Pure-Bind, Pure-Coat, Pure-Gel and Pure-Set (Grain Processing Corp.) are tradenames for modified starches.