Oral osmotically driven systems: 30 years of development and clinical use

doi:10.1016/j.ejpb.2009.07.002

European Journal of Pharmaceutics and Biopharmaceutics

Volume 73, Issue 3, November 2009, Pages 311-323

https://doi.org/10.1016/j.ejpb.2009.07.002 Get rights and content

Abstract

The number of marketed oral osmotically driven systems (OODS) has doubled in the last 10 years. The main clinical benefits of OODS are their ability to improve treatment tolerability and patient compliance. These advantages are mainly driven by the capacity to deliver drugs in a sustained manner, independent of the drug chemical properties, of the patient’s physiological factors or concomitant food intake. However, access to these technologies has been restricted by the crowded patent landscape and manufacturing challenges. In this review article, we intend to give an overview of the OODS development in the last 30 years, detailing the technologies, specific products and their clinical use. General guidance on technology selection is described in light of the recent advances in the field. The clinical performance of these technologies is also discussed, with a focus on food effects and the in vivo–in vitro correlation. Special attention is paid to safety given the controversial case study of Osmosin^®. Overall, oral osmotically driven systems appear to be a promising technology for product life-cycle strategies.

Section snippets

Overview on 30 years of OODS development

Controlled drug delivery has taken an important place in pharmaceutical development, improving the tolerability and patient compliance with prescribed dosing regimens [1], [2], [3]. Despite the predominant use of polymer-based systems, alternatives have been developed to decrease the influence of the various physiological factors that occur following food intake or that are dependent on patient age [2], [3], [4]. One of the most promising technologies is the oral osmotically driven system

Literature review

The information sources dealing with OODS are relatively restricted and are often limited with respect to full retrieval of all technical details. As described in Fig. 2, information has been mainly obtained through intellectual property (IP) publications, which to some extent, are difficult to analyze and judge [30]. Only 14 research papers were published on the formulation aspects of osmotic systems versus 161 patents on the same topic until the year 2000. In 90%, of these, Alza Corp.

Technology panel and selection

Ideally, the selection of the OODS technology needs to be done with consideration for the desired pharmacokinetic profile of the drug product. The approach is to control the drug plasma profile by managing the drug release kinetics from the OODS as shown in Fig. 3. To a large extent, the formulation strategy is based on the biopharmaceutical classification (BCS) of a particular drug substance, as proposed by Corrigan and Amidon [40], [41], [42] and illustrated in Fig. 4: Only drugs with a high

Safety and precautions

In discussing the development of the OODS, one main safety aspect must be addressed as a prerequisite—the drug substance irritant property to the target site. Thus, in the case of the delivery of irritating drug substances, the concern is over the local delivery of the drug from an OODS with impaired transit through the GI tract, which might lead to gut wall irritations. In the worst case, it can result in gut wall perforations, as has been reported from patients receiving the indomethacin

Conclusion

Development efforts of oral osmotically driven systems (OODSs) during recent years have been very dynamic with the emergence of new technologies and products. With the expiration of the OODS primary patents and the increasing demand of health authorities for improved patient treatment compliance and tolerability, the OODS is primed to increase their market within oral modified-release dosage forms. Developed as a drug delivery platform for delivering drugs regardless of their physico-chemical

Acknowledgement

The authors are thankful to Drs Patrice Guitard, Dilraj Singh and Dieter Becker, Novartis Pharma, Basel, Switzerland, for the stimulating discussions and scientific contributions.

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Cellulose acetate (CA) is the main component of controlled-release (CR) coating of formulations such as osmotic-controlled release oral delivery system (OROS) and CR microspheres. Despite multiple applications, there are limited or no reports dealing with the characterization and quantification of CA in the formulated systems. Thus, the present investigation deals with the development of the Quantitative Carbon-13 Nuclear Magnetic Resonance (q¹³CNMR) spectroscopy method for the determination of CA amount in the CR microsphere formulations. The developed q¹³CNMR method was also verified using control CA samples from marketed OROS formulation. Thereafter, the concentration of CA in the microspheres was calculated. Furthermore, the impact of different concentrations of CA on the critical quality attributes such as the drug release profile from the formulation was investigated. The study demonstrated the CA coating levels to be inversely proportional to the extent and rate of release of API. The developed q¹³CNMR method was found to be accurate and precise and can be explored further to investigate the effect of different stability conditions on the degree of polymerization and degradation of CA resulting in altered quality of pharmaceutical products.
Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism
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Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral “roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.
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In recent years, oral osmotic tablets have sparked a therapeutic paradigm for controlled-release dosage forms due to their intrinsic insensitivity to physiological and physicochemical factors. Despite these benefits, the design of an optimal osmotic technology is precluded by various challenges. These limitations include manufacturing complexity, the lack of understanding of the functional mechanics, and inadequate optimization for the desired bio-performance. This paper systematically reviews the development of an osmotic-driven drug delivery system and the strategy for a zero-order release profile with an emphasis on swellable core technology. We discuss the applicability of the various types of osmotic tablets, their suitability to specific needs, and factors that drive the technology selection. Finally, we review the challenges, opportunities, and future perspectives associated with osmotic tablets.
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Review articleOral osmotically driven systems: 30 years of development and clinical use

Abstract

Section snippets

Overview on 30 years of OODS development

Literature review

Technology panel and selection

Safety and precautions

Conclusion

Acknowledgement

J. Pharm. Sci.

J. Control. Rel.

J. Pharm. Sci.

Pathol. Res. Pract.

Toxicol. Appl. Pharmacol.

Lancet

Lancet

J. Control. Rel.

J. Control. Rel.

Drug Disc. Today

Eur. J. Pharm. Biopharm.

Int. J. Pharm.

Int. J. Pharm.

J. Control. Rel.

J. Pharm. Sci.

J. Pharm. Sci.

Eur. J. Pharm. Biopharm.

Int. J. Pharm.

Eur. J. Pharm. Biopharm.

J. Control. Rel.

Int. J. Pharm.

Overview of oral modified-release opioid products for the management of chronic pain

Ann. Pharmacother.

Drug delivery systems for treatment of systemic hypertension

Clin. Pharmacokinet.

Calcium-antagonists in cardiology – update on sustained-release drug delivery systems

Clin. Cardiol.

Clinical spectrum of the osmotic-controlled release oral delivery system (OROS), an advanced oral delivery form

Curr. Med. Res. Opin.

The nifedipine gastrointestinal therapeutic system (GITS). Evaluation of pharmaceutical, pharmacokinetic and pharmacological properties

Clin. Pharmacokinet.

Gastrointestinal safety of an extended-release, nondeformable, oral dosage form (OROS (R)) – a retrospective study

Drug Saf.

A continuous long-term injector

Aust. J. Exp. Biol.

Phenylpropanolamine OROS (Acutrim) vs. placebo in combination with caloric restriction and physician-managed behavior modification

Clin. Pharmacol. Ther.

Gits – a new medicine administration system

Zeit. Rheum.

Pharmacokinetics of indomethacin gits (osmotically controlled delivery system)

Aust. NZ. J. Med.

The gastro intestinal therapeutic systems (gits) for indomethacin to decrease side-effects

Aust. NZ. J. Med.

Intestinal perforation associated with osmotic slow release indomethacin capsules

Br. Med. J.

Indomethacin and perforated duodenal ulcer

Br. Med. J.

Studies on the cumulation of the toxic effect of indomethacin

Pol. Med. Sci. Hist. Bull.

Drug induced ulceration and perforation of the small intestine

Ariz. Med.

P+T committee review of nifedipine gits – new modality for angina and hypertension

Hosp. Form.

Long-term protection in at-risk hypertensive patients – a role for nifedipine GITS?

Blood Press

nifedipine gits (gastrointestinal therapeutic system) bezoar

Arch. Int. Med.

Small bowel procardia XL tablet bezoar mimicking cystic pneumatosis intestinalis

Abdom. Imag.

Osmotic, controlled-release methylphenidate for the treatment of ADHD

Expert Opin. Pharmacother.

An update on osmotic drug delivery patents

Pharm. Tech.

An overview of recent patents on oral osmotic drug delivery systems

Recent Patent Drug Del. Form.

Osmotically controlled oral drug delivery

Drug Dev. Ind. Pharm.

Osmotic pumps in drug delivery

Crit Rev. Ther. Drug Carrier Syst.

The unique adalat story – nifedipine gastrointestinal therapeutic system

Eur. Cardiovasc. Dis.

Review article
Oral osmotically driven systems: 30 years of development and clinical use