Evaluation of an intestinal pressure-controlled colon delivery capsules prepared by a dipping method.
A new method for preparation of large amounts of empty pressure-controlled colon delivery capsules (PCDCs) by a dipping method has been developed. Empty PCDCs are composed of two polymer membranes. The inner one was a water-insoluble polymer membrane, ethylcellulose (EC). The outer one was an enteric polymer membrane, hydroxypropylmethylcellulose phthalate (HPMCP) or hydroxypropylmethylcellulose acetate succinate (HPMCAS). By consequently dipping into an ethanolic EC solution and an alkalized enteric polymer solution, empty PCDCs were obtained after both the capsule body and cap were adjusted to the size of #2 capsules. With each enteric polymer, two types of empty PCDCs of different thickness were prepared. Fluorescein (FL) was formulated with suppository base, PEG1000, and used as a model drug. FL/PEG1000 suspension was introduced into empty PCDCs which were then sealed with enteric polymer solution. The PCDCs were evaluated by an in vivo experiment using beagle dogs. After oral administration of the test PCDC preparations containing 30 mg of FL, blood samples were obtained from the jugular vein and serum FL levels were measured. The thickness of the EC membrane layer varied in both the capsule body and cap. HPMCAS PCDCs had 62.1+/-5.0 (S.E.) microm (body) and 49.7+/-3.3 microm (cap) with thicker ones and 55.7+/-6.6 microm (body) and 46.8+/-6.2 microm (cap) with thinner ones. HPMCP PCDCs had 28.1+/-3.3 microm (body), 30.9+/-1.0 microm (cap) with thinner ones and 43.1+/-9.8 microm (body), 42.4+/-8.2 microm (cap) with thicker ones. The mean T(i) values, the first appearance time, of FL in the serum of HPMCAS PCDCs were 2.0+/-0.7 h for thicker ones and 3.8+/-0.5 h for thinner ones, while the mean T(i) values of HPMCP PCDCs were 2.0+/-0.0 h for thinner ones and 3.5+/-0.7 h for thicker ones. Since the colon arrival time in beagle dogs was 3.5+/-0.3 h as determined by a sulfasalazine test, thinner HPMCAS PCDCs and thicker HPMCP PCDCs were thought to deliver FL to the colon.
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8414, Kyoto, Japan.
Y I
YI
Jeong
T
T
Ohno
Z
Z
Hu
Y
Y
Yoshikawa
N
N
Shibata
S
S
Nagata
K
K
Takada
D000818:Animals; D019540:Area Under Curve; D002214:Capsules / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003106:Colon; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D019793:Fluorescein / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry*; D012597:Sclerosing Solutions / Q000737:chemistry
D002214:Capsules; D003287:Contrast Media; D005079:Excipients; D012597:Sclerosing Solutions; C048331:hydroxypropylmethylcellulose acetate succinate; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D019793:Fluorescein