Hydroxypropyl Methylcellulose (Hypromellose/HPMC) Safety in Pharmaceuticals
Hydroxypropyl methylcellulose (hypromellose/HPMC) is safe for use in pharmaceutical formulations, with an established FDA approval as both a direct and indirect food additive, an EU approval for food use, and a JECFA acceptable daily intake (ADI) designation of "not specified," indicating no safety concerns at typical exposure levels. 1
Regulatory Status and Safety Assessment
- FDA has approved HPMC as both a direct and indirect food additive, establishing its safety profile for pharmaceutical applications 1
- The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has assigned an ADI of "not specified" for HPMC, which is the most favorable safety designation indicating no toxicological concerns at expected consumption levels 1
- The European Union has approved HPMC for use as a food additive, further supporting its international safety recognition 1
Toxicological Safety Data
- The no-observed-adverse-effect level (NOAEL) from a 90-day rat feeding study was 5000 mg/kg body weight/day, demonstrating a very high safety margin 1
- The tolerable intake for humans is established at 5 mg/kg body weight/day, which is more than 100-fold greater than the estimated current consumption of 0.047 mg/kg body weight/day 1
- This safety margin provides substantial protection even with increased pharmaceutical use beyond typical dietary exposure 1
Pharmaceutical Applications Demonstrating Safety
- HPMC is widely used as a stabilizer in drug nanocrystals without evidence of toxicity concerns 2
- HPMC serves as a viscosity-enhancing agent in endoscopic lifting solutions and other medical procedures 2
- The compound functions as an excipient in capsule shells, successfully replacing animal-derived gelatin without safety issues 3
- HPMC is employed in ocular drug delivery formulations including eye drops, injections, films, and inserts, demonstrating biocompatibility in sensitive tissues 4
- Low-viscosity grades (E3 and E5) are used as physical modifiers for pharmaceutical powders to improve flowability, compressibility, and stability 5
Important Clinical Considerations
- HPMC can form molecular-level interactions with certain drugs (such as naproxen), which may affect drug stability and should be evaluated during formulation development 2
- Drug-excipient compatibility testing is essential when HPMC is used as a stabilizer, as interactions can lead to degradation in specific cases (e.g., naproxen showed degradation with HPMC but not with Tween 80) 2
- Minimal cross-reactivity exists with other celluloses (such as carboxymethylcellulose), making allergic reactions extremely rare 2
- No special monitoring is required for patients receiving pharmaceutical products containing HPMC, as it is generally well-tolerated without significant adverse effects 1
Biocompatibility Profile
- HPMC is biocompatible, uncharged, water-soluble, and exhibits thermoplastic behavior, making it suitable for diverse pharmaceutical applications 4
- The compound is odorless, tasteless, and derived from natural cellulose polymer, contributing to its excellent tolerability profile 1
- HPMC demonstrates excellent mucoadhesive properties, supporting its use in oral and oromucosal delivery systems without safety concerns 6