Effects on Offspring Induced by Oral Administration of Hydroxypropylmethylcellulose Acetate Succinate to the Female Rats in Peri-and Post-Natal Periods

Embryo/fetal development studies with hydroxypropyl methylcellulose acetate succinate (HPMCAS) in rats and rabbits

“…First, clubfoot was only noted for fetuses evaluated after cesarean section. In the same study, there were no findings of clubfoot for offspring after natural delivery (Hoshi et al, 1985c) nor were there any clubfoot in the peri‐ and postnatal development study (Hoshi et al, 1985a), even though clubfoot would not be expected to be a lethal developmental anomaly. Second, the historical control incidence for clubfoot in rats is 0.001% in the United States (Charles Rivers Laboratories, 1995) and 0.006% in Japan (Morita et al, 1987).…”

“…Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is a cellulose‐based excipient that has been evaluated for use in multiple strategies to increase drug bioavailability including use as an enteric coating, as a polymer in sustained and controlled release formulations, and in dosage forms designed to achieve long intragastric retention and to target drug release to the colon (Hilton and Deasy, 1993; Obara and McGinity, 1994, Obara et al, 1999; Fukui et al, 2001a–c; Nakamichi et al, 2001). In addition to its physical characteristics, HPMCAS is considered a useful excipient because of low bioavailability and lack of toxicity in preclinical evaluations (Hoshi et al, 1985a–f).…”

“…The potential for HPMCAS to produce developmental and reproductive toxicity was evaluated in a series of studies that included rat and rabbit teratology studies, a rat fertility study, and a rat peri‐ and postnatal study (Hoshi et al, 1985a–c). The authors concluded that there were no compound‐related findings.…”

Pharmacobezoar Formation From HPMC-AS-Containing Spray-Dried Formulations in Nonclinical Safety Studies in Rats

“…HPMC-AS has been examined with regard to acute, subchronic, and chronic toxicological effects in a battery of studies by Hoshi et al. 16 -20 As HPMC-AS was found to be only poorly absorbed and toxicologically relevant effects were absent at doses up to 2500 mg/kg/day in rats, HPMC-AS was recognized as safe for use in nonclinical studies. For pharmaceutical use, for example, as a carrier for ASDs, it even gained the GRAS status provided by the United States Food and Drug Administration.…”

“…In some cases, surfactants like sodiumdodecylsulfate (SDS) or viscosity enhancers such as hydroxyethylcellulose (HEC) may be added to the vehicle to improve wettability of the SD-ASDs and homogeneity of the suspension. 5,15 HPMC-AS has been examined with regard to acute, subchronic, and chronic toxicological effects in a battery of studies by Hoshi et al [16][17][18][19][20] As HPMC-AS was found to be only poorly absorbed and toxicologically relevant effects were absent at doses up to 2500 mg/kg/day in rats, HPMC-AS was recognized as safe for use in nonclinical studies. For pharmaceutical use, for example, as a carrier for ASDs, it even gained the GRAS status provided by the United States Food and Drug Administration.…”