OROS Safety and Clinical Aspects

Benefits of osmosis-driven technology relate to its capability to:

• Release drug at a constant (zero order) rate.

• Provide consistent release regardless of drug or environment, i.e., independent of drug, patient physiology, or food effect [9].

• Sustain delivery over a significant time period.

• Pulse and/or delay delivery to align with patient needs or mode of drug action.

Treatment tolerability and patient compliance may improve with some medications as a consequence of such delivery. OROS™ technology, with its capability to provide lower peak plasma levels and "smoother" plasma profiles

Fig. 6.5 OSMODEX

system

Fig. 6.5 OSMODEX

system

may also result in reduced plasma level-related side effects [10]. Wonnemann et al. compared the bioavailability of nifedipine from two commercial modified release nifedipine products, viz., Adalat OROS 30™ and Nifedipine Retard 30™. A significant food interaction effect was noted with Nifedipine Retard 30™. In contrast, food intake did not have a significant effect on release from the OROS™ dosage form, based on pharmacokinetic parameters. Variable and unpredictable plasma levels, suggestive of inconsistent delivery were also noted with the Nifedipine Retard 30™ formulation. Such findings illustrate the hazard of switching medications that might ostensibly seem to have comparable efficacy and safety [11].

Sathyan et al. reported that side effects associated with immediate-release oxy-butinin can be alleviated using an extended release OROS™ presentation of the drug [12]. Paliperidone is an oral psychotropic agent for treating schizophrenia. It undergoes limited hepatic metabolism if formulated utilizing OROS technology. Davidson et al. studied safety and efficacy of once-daily paliperidone in acute schizophrenia. All doses of extended-release paliperidone were well tolerated and shown to improve personal and social functioning [13]. In another clinical study in acute schizophrenia, symptoms were improved significantly in patients who used paliperidone ER [14].

Potential drawbacks associated with the OROS™ platforms include the high costs of manufacture (laser drilling is required). Dose dumping is also a potential issue if the semipermeable coat is compromised as the entire daily dose being contained in a single unit. Bass et al. comprehensively reviewed safety aspects of tablets based on OROS™ technology. Long-term safety data indicated a low incidence of clinically significant GI tract side effects including intestinal, gastric, and esophageal irritation, injury, and obstruction. The general experience indicates that for some drugs OROS™-based products can provide substantial therapeutic and convenience benefits without delivery-related risks [15].

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