Peroral Absorption of Octreotide in Pigs Formulated in Delivery Systems on the Basis of Superporous Hydrogel Polymers

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2002 Nov 12

PMID 12425472

Citations 8

Authors

Farid A Dorkoosh

J Coos Verhoef

Jos H M Verheijden

Morteza Rafiee-Tehrani

Gerrit Borchard

Hans E Junginger

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of this study was to investigate the enhancement of peroral octreotide absorption using delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) polymers.

Methods: Six female pigs (BW of 23.5 kg) were used in this study. SPH-based delivery systems were made of two components: 1) a conveyor system made of SPH and SPHC; 2) a core that contained octreotide. The core was inserted into the conveyor system (core inside, c.i.) or attached to the surface of the conveyor system (core outside, c.o.). Four different peroral formulations were investigated: c.i., c.o., core outside including trimethyl chitosan chloride (c.o.t.), and octreotide only in the absence of any polymer (o.o.). All formulations were placed in enteric-coated gelatin capsules (size 000) and administered perorally. Intravenous administration was used to determine bioavailability (F) values. Blood samples taken from the cannulated jugular vein were analyzed by radioimmunoassay.

Results: Peroral administration of 15 mg o.o. resulted in low F values of 1.0 +/- 0.6% (mean +/- SEM) whereas c.i. and c.o. administrations resulted in remarkably higher F values of 12.7 +/- 3.6% and 8.7 +/- 2.4%, respectively. By the addition of trimethyl chitosan chloride as an extra absorption enhancer to c.o.t., the highest bioavailability (16.1 +/- 3.3%) was achieved.

Conclusions: These novel delivery systems based on SPH and SPHC polymers are able to increase the peroral bioavailability of octreotide by mechanical fixation and increasing the retention of the dosage form at the absorption site.

Citing Articles

Flexible Coatings Facilitate pH-Targeted Drug Release via Self-Unfolding Foils: Applications for Oral Drug Delivery.

Milian-Guimera C, De Vittorio L, McCabe R, Goncu N, Krishnan S, Eklund Thamdrup L Pharmaceutics. 2024; 16(1).

PMID: 38258092 PMC: 10819044. DOI: 10.3390/pharmaceutics16010081.

Application of Permeation Enhancers in Oral Delivery of Macromolecules: An Update.

Maher S, Brayden D, Casettari L, Illum L Pharmaceutics. 2019; 11(1).

PMID: 30669434 PMC: 6359609. DOI: 10.3390/pharmaceutics11010041.

Role of Mechanical Factors in Applications of Stimuli-Responsive Polymer Gels - Status and Prospects.

Goponenko A, Dzenis Y Polymer (Guildf). 2017; 101:415-449.

PMID: 28348443 PMC: 5365095. DOI: 10.1016/j.polymer.2016.08.068.

Hydrogel: Preparation, characterization, and applications: A review.

Ahmed E J Adv Res. 2015; 6(2):105-21.

PMID: 25750745 PMC: 4348459. DOI: 10.1016/j.jare.2013.07.006.

Development of bioadhesive chitosan superporous hydrogel composite particles based intestinal drug delivery system.

Chavda H, Modhia I, Mehta A, Patel R, Patel C Biomed Res Int. 2013; 2013:563651.

PMID: 23984380 PMC: 3747347. DOI: 10.1155/2013/563651.

References

Digenis G, Sandefer E, Page R, Doll W, Gold T, Darwazeh N . Bioequivalence study of stressed and nonstressed hard gelatin capsules using amoxicillin as a drug marker and gamma scintigraphy to confirm time and GI location of in vivo capsule rupture. Pharm Res. 2000; 17(5):572-82. DOI: 10.1023/a:1007568900147. View

Ottesen L, Aagaard N, Kiszka-Kanowitz M, Rehling M, Henriksen J, Pedersen E . Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial. Hepatology. 2001; 34(3):471-7. DOI: 10.1053/jhep.2001.26754. View

Ameye D, Voorspoels J, Foreman P, Tsai J, Richardson P, Geresh S . Trypsin inhibition, calcium and zinc ion binding of starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures for peroral peptide drug delivery. J Control Release. 2001; 75(3):357-64. DOI: 10.1016/s0168-3659(01)00408-4. View

Thanou M, Verhoef J, Verheijden J, Junginger H . Intestinal absorption of octreotide using trimethyl chitosan chloride: studies in pigs. Pharm Res. 2001; 18(6):823-8. DOI: 10.1023/a:1011092613951. View

Chen J, Park K . Synthesis and characterization of superporous hydrogel composites. J Control Release. 2000; 65(1-2):73-82. DOI: 10.1016/s0168-3659(99)00238-2. View

Dorkoosh F, Verhoef J, Borchard G, Rafiee-Tehrani M, Junginger H . Development and characterization of a novel peroral peptide drug delivery system. J Control Release. 2001; 71(3):307-18. DOI: 10.1016/s0168-3659(01)00232-2. View

Zhou S, Deng X, Li X . Investigation on a novel core-coated microspheres protein delivery system. J Control Release. 2001; 75(1-2):27-36. DOI: 10.1016/s0168-3659(01)00379-0. View

Fix J . Oral controlled release technology for peptides: status and future prospects. Pharm Res. 1996; 13(12):1760-4. DOI: 10.1023/a:1016008419367. View

Dorkoosh F, Setyaningsih D, Borchard G, Rafiee-Tehrani M, Verhoef J, Junginger H . Effects of superporous hydrogels on paracellular drug permeability and cytotoxicity studies in Caco-2 cell monolayers. Int J Pharm. 2002; 241(1):35-45. DOI: 10.1016/s0378-5173(02)00115-1. View

10.

Dorkoosh F, Verhoef J, Ambagts M, Rafiee-Tehrani M, Borchard G, Junginger H . Peroral delivery systems based on superporous hydrogel polymers: release characteristics for the peptide drugs buserelin, octreotide and insulin. Eur J Pharm Sci. 2002; 15(5):433-9. DOI: 10.1016/s0928-0987(02)00028-3. View

11.

Harrigan R, Nathan M, Beattie P . Oral agents for the treatment of type 2 diabetes mellitus: pharmacology, toxicity, and treatment. Ann Emerg Med. 2001; 38(1):68-78. DOI: 10.1067/mem.2001.114314. View

12.

Marbach P, Neufeld M, Pless J . Clinical applications of somatostatin analogs. Adv Exp Med Biol. 1985; 188:339-53. DOI: 10.1007/978-1-4615-7886-4_19. View

13.

Dorkoosh F, Borchard G, Rafiee-Tehrani M, Verhoef J, Junginger H . Evaluation of superporous hydrogel (SPH) and SPH composite in porcine intestine ex-vivo: assessment of drug transport, morphology effect, and mechanical fixation to intestinal wall. Eur J Pharm Biopharm. 2002; 53(2):161-6. DOI: 10.1016/s0939-6411(01)00222-3. View

14.

Davis S . Delivery systems for biopharmaceuticals. J Pharm Pharmacol. 1992; 44 Suppl 1:186-90. View

15.

Takacs T, Hajnal F, Nemeth J, Lonovics J, Pap A . Stimulated gastrointestinal hormone release and gallbladder contraction during continuous jejunal feeding in patients with pancreatic pseudocyst is inhibited by octreotide. Int J Pancreatol. 2001; 28(3):215-20. DOI: 10.1385/IJGC:28:3:215. View

16.

Thanou M, Verhoef J, Marbach P, Junginger H . Intestinal absorption of octreotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. J Pharm Sci. 2000; 89(7):951-7. DOI: 10.1002/1520-6017(200007)89:7<951::AID-JPS13>3.0.CO;2-1. View

17.

Parr A, Sandefer E, Wissel P, McCartney M, McClain C, Ryo U . Evaluation of the feasibility and use of a prototype remote drug delivery capsule (RDDC) for non-invasive regional drug absorption studies in the GI tract of man and beagle dog. Pharm Res. 1999; 16(2):266-71. DOI: 10.1023/a:1018884510163. View

18.

Schiedermaier P, Goke B, Sauerbruch T . Effects of different octreotide dosages on splanchnic hemodynamics and glucagon in patients with TIPS. Am J Gastroenterol. 2001; 96(7):2218-24. DOI: 10.1111/j.1572-0241.2001.03960.x. View

19.

Damge C, Vonderscher J, Marbach P, Pinget M . Poly(alkyl cyanoacrylate) nanocapsules as a delivery system in the rat for octreotide, a long-acting somatostatin analogue. J Pharm Pharmacol. 1997; 49(10):949-54. DOI: 10.1111/j.2042-7158.1997.tb06022.x. View