Issue link: https://www.e-digitaleditions.com/i/1481708
PharmTech.com Trends in Formulation 2022 eBook Pharmaceutical Technology ® 21 injections. In 1992, researchers at the University of Cin- cinnati reported that children with severe cholestasis exhibited enhanced absorption of vitamin D3 co-ad- ministered with TPGS (4). Sokol (5) then observed that TPGS enhanced the absorption of cyclosporin—an im- munosuppressant drug required in huge doses to treat pediatric liver transplant patients—and several other groups reported similar findings (6,7). This early work provided the impetus for additional studies into the enhancement of solubility and absorption and many new and interesting properties began to emerge. In 1999, FDA approved the first drug using TPGS: Am- prenavir, a protease inhibitor used in the treatment of HIV patients (8). Today, TPGS is a powerful tool for formulators in a wide variety of industries and is used to improve the solubility and bioavailability of many lipophilic and poorly soluble bioactive materials. Properties of TPGS Vitamin E TPGS (Figure 1) is the mixed ester formed by the reaction of succinic anhydride with natural vi- tamin E and polyethylene glycol (PEG) 1000. This am- phiphilic skeleton results in TPGS having significant solubility in water, approximately 200 g/L, which is around 100 times higher than that of the α-tocopherol (21 mg/L). TPGS has an average molecular weight of 1513 g/mol and with a melting range of 37–41 °C, it is a waxy solid at room temperature. TPGS delivers 387 IU/g of natural vitamin E when used as a nutritional supplement and is stable to most processing conditions including sterilization treatment. Its calculated hydro- philic/lipophilic balance (HLB) number of 13.2 enables TPGS to act as an oil-in-water emulsifier, and while early applications have been focused on this property, TPGS can also function as a solubilizer, absorption en- hancer, stabilizer, and permeation enhancer in a vari- ety of biomedical and nutraceutical applications. Delivery forms TPGS is used to deliver products in a wide variety of industries including pharmaceuticals, dietary sup- plements, personal care and cosmetics, food and bev- erage, and animal nutrition and health. TPGS can be incorporated into product forms such as liquid for- mulations, capsules, chewable tablets, nutrition bars, gummies, drops, bottled beverages and sports drinks, sprays, and drops. In addition to these oral admin- istration routes, TPGS can be used in topical, nasal, ophthalmic, and parenteral applications, as well as in a new generation of nanoparticles developed for targeted cell and tissue delivery. TPGS safety and manufacturing status The safety of TPGS has been evaluated thoroughly by several institutes, including the National Cancer Insti- tute, the National Institutes of Health, the Cystic Fibro- sis Foundation, and other research organizations (9–11). Major clinical studies in humans have ascertained its safety for use in foods and beverages, dietary supple- ments, personal care products, and medical food and drug formulations. An extensive review of the work that led to the approval of TPGS in foods for special medical purposes is available in the Opinion of the Scientific Panel European Food Safety Authority (12). A summary of TPGS's safety characteristics is shown in Table I. It is possible to purchase TPGS that is manufactured under current good manufacturing practices (CGMP) 21 Code of Federal Regulations (CFR) 210 and complies with the International Excipients Council (IPEC) and Pharmaceutical Quality Groups (PQG) manufactur- ing guidelines for pharmaceutical excipients. TPGS manufactured by Antares is available in both food grade (FG) and pharmaceutical grade (NF) and can also be purchased as a non-GMO material that is derived from sunf lowers. All grades are provided in tamper evident containers of various sizes and is stored and distributed under IPEC Good Distribution Practices (IPEC-GDP). BCS classification of new chemical entities Pharmacokinetics—the branch of pharmacology con- cerned with the movement and disposition of drugs Figure 1. Vitamin E TPGS FIGURE 1. Vitamin E TPGS. Formul ation and drug delivery FIGURES COURTESY OF THE AUTHOR.