Formulation development for cancer compounds – Biopharmaceutical issues and perspectives

Nuggehally R Srinivas

Abstract


The development of formulations for anti-cancer drugs imposes challenges owing to the different physicochemical attributes of the compounds as well as the need to deliver the compound to the desired target and/or tumor sites. In this article
we present case studies to discuss recent formulation related work for both paclitaxel and topotecan. As enumerated by the case studies, biopharmaceutical and pharmacokinetic challenges are imposed in design and optimization of suitable dosage forms for both intravenous and oral drug delivery. The focus is on selection of excipients which may play additional role(s) in contributing towards the disposition of both paclitaxel and topotecan.


Full Text:

PDF

References


Cheong I, Huang X, Thornton K, Diaz LA Jr, Zhou S. Targeting cancer

with bugs and liposomes: Ready, aim, fire. Cancer Res 2007;20:9605-8.

Cavalieri F, Chiessi E, Villa R, Viganò L, Zaffaroni N, Telling MF,

Paradossi G. Novel PVA-based hydrogel microparticles for doxorubicin

delivery. Biomacromolecules 2008;9:1976-3.

You JO, Auguste DT. Feedback-regulated paclitaxel delivery based

on poly(N,N-dimethylaminoethylmethacrylate-co-2-hydroxyethyl

methacrylate) nanoparticles. Biomaterials 2008;29:1950-7.

Bielawski K, Bielawska A. Small-molecule based delivery systems for

alkylating antineoplastic compounds. Chem Med Chem 2008;3:536-42.

Nornoo AO, Zheng H, Lopes LB, Johnson-Restrepo B, Kannan K, Reed R.

Oral microemulsions of paclitaxel: In situ and pharmacokinetic studies.

Eur J Pharm Biopharm 2009;71:310-7.

Ben Reguiga M, Bonhomme-Faivre L, Farinotti R. Bioavailability and

tissular distribution of docetaxel, a P-glycoprotein substrate, are

modified by interferon-alpha in rats. J Pharm Pharmacol 2007;59:401-8.

Breedveld P, Beijnen JH, Schellens JH. Use of P-glycoprotein and BCRP

inhibitors to improve oral bioavailability and CNS penetration of

anticancer drugs. Trends Pharmacol Sci 2006;27:17-24.

Chu Z, Chen JS, Liau CT, Wang HM, Lin YC, Yang MH, et al. Oral

bioavailability of a novel paclitaxel formulation (Genetaxyl) administered

with cyclosporin A in cancer patients. Anti-Cancer Drugs 2008;19:275-81.

Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, Yang A, et al.

Comparative preclinical and clinical pharmacokinetics of a cremophor-

free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel

formulated in Cremophor (Taxol). Clin Cancer Res 2005;11:4136-43.

Malingre MM, Schellens JH, Van Tellingen O, Ouwehand M, Bardelmeijer HA, Rosing H, et al. The co-solvent Cremophor EL limits oral absorption of orally administered paclitaxel in cancer patients. Br J Cancer 2001;85:1472-7.

Yamagata T, Kusuhara H, Morishita M, Takayama K, Benameur H,

Sugiyama Y. Improvement of the oral drug absorption of topotecan throughthe inhibition of intestinal xenobiotic efflux transporter, breast cancer resistance protein, by excipients. Drug Metab Dispos 2007;35:1142-8.

Joerger M, Huitema AD, van den Bongard DH, Schellens JH, Beijnen JH.Quantitative effect of gender, age, liver function and body size on the

population pharmacokientics of paclitaxel in patients with solid tumors.

Clin Cancer Res 2006;12:2150-7.

Karlsson MO, Molnar V, Freijs A, Nygren P, Bergh J, Larsson R.

Pharmacokinetic models for the saturable distribution of paclitaxel.

Drug Metab Dispos 1999;27:1220-3.

Kearns CM, Gianni L, Egorin MJ. Paclitaxel pharmacokinetics and

pharmacodynamics. Semin Oncol 1995;22:16-23.

Sonnichsen DS, Hurwitz CA, Pratt CB, Shuster JJ, Relling MV. Saturable

pharmacokinetics and paclitaxel pharmacodynamics in children with

solid tumors. J Clin Oncol 1994;12:532-8.

Henningson A, Karlsson MO, Vigano L, Gianni L, Verweij J, Sparreboom A. Mechanism-based pharmacokinetic model for paclitaxel. J Clin Oncol

;19:4065-73.

Henningson A, Sparreboom A, Sandstrom M, Freijs A, Larsson R, Bergh J,et al. Population pharmacokinetic modelling of unbound and total

plasma concentrations of paclitaxel in cancer patients. Eur J Cancer

;39:1105-14.

Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JH. Nonlinear

pharmacokinetics of paclitaxel in mice results from the pharmaceutical

vehicle Cremophor EL. Cancer Res 1996;56:2112-5.

Sparreboom A, van Zuylen L, Brouwer E, Loos WJ, de Bruijin P,

Gelderblom H, et al. Cremophor EL-mediated alteration of paclitaxel

distribution in human blood: Clinical pharmacokinetic implications.

Cancer Res 1999;59:1454-7.

Bullita JB, Zhao P, Arnold RD, Kessler DR, Daifuku R, Pratt J, et al.

Mechanistic population of pharmacokinetics of total and unbound

paclitaxel for a new nanodroplet formulation versus taxol in cancer

patients. Cancer Chemother Pharmacol 2009;63:1049-63.

Stewart CF, Leggas M, Schuetz JD, Panetta JC, Cheshire PJ, Peterson J,

et al. Geftinib enhances the antitumor activity and oral bioavailability

of irinotecan in mice. Cancer Res 2004;64:7491-9.

Varma MV, Panchagnula R. Enhanced oral paclitaxel absorption with

vitamin E-TPGS: Effect on solubility and permeability in vitro, in situ

and in vivo. Eur J Pharm Sci 2005;25:445-53.

Yamagata T, Kusuhara H, Morishita M, Takayama K, Benameur H,

Sugiyama Y. Effect of excipients on breast cancer resistance protein

substrate uptake activity. J Control Release 2007;124:1-5.

Brown TJ. The development of hyaluronan as a drug transporter

and excipient for chemotherapeutic drugs. Curr Pharm Biotechnol

;9:253-60.

Lee L, Hossain M, Wang Y, Sedek G. Absorption of rivastigmine

from different regions of the gastrointestinal tract in humans. J Clin

Pharmacol 2004;44:599-604.

Srinivas NR, Shyu WC, Greene DS, Barbhaiya RH. Oral absorption of

BMS-181101, an anti-depressant, from the various gastrointestinal

regions of healthy human subjects. J Appl Ther Res 2001;3:7-18.

Kelly K, O’Mahony B, Lindsay B, Jones T, Grattan TJ, Rostami-Hodjegan A, et al. Comparison of the rates of disintegration, gastric emptying, and drug absorption following administration of a new and a conventiomalparacetamol formulation, using gamma scintigraphy. Pharm Res2003;20:1668-73.

Oo C, Snell P, Barrett J, Dorr A, Liu B, Wilding I. Pharmacokinetics and

delivery of the anti-influenza prodrug oseltamivir to the small intestine

and colon using site-specific capsules. Int J Pharm 2003;257:297-9.




DOI: http://dx.doi.org/10.22377/ajp.v3i2.247

Refbacks

  • There are currently no refbacks.