Joerg Ogorka

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

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 patients 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.

Benchtop-magnetic resonance imaging (BT-MRI) characterization of push–pull osmotic controlled release systems

The mechanism of drug release from push-pull osmotic systems (PPOS) has been investigated by Magnetic Resonance Imaging (MRI) using a new benchtop apparatus. The signal intensity profiles of both PPOS layers were monitored non-invasively over time to characterize the hydration and swelling kinetics. The drug release performance was well-correlated to the hydration kinetics. The results show that (i) hydration and swelling critically depend on the tablet core composition, (ii) high osmotic pressure developed by the push layer may lead to bypassing the drug layer and incomplete drug release and (iii) the hydration of both the drug and the push layers needs to be properly balanced to efficiently deliver the drug. MRI is therefore a powerful tool to get insights on the drug delivery mechanism of push-pull osmotic systems, which enable a more efficient optimization of such formulations.

Approach to design push–pull osmotic pumps

Despite more than 30 years of clinical use, only few studies have been published reporting on the release mechanism underlying the drug delivery from push-pull osmotic pumps (PPOP). The aim of this study is to understand which factors have an effect on the drug delivery for modelling the drug release and to develop a mathematical model predictive of the drug release kinetics. The influence of the drug property was tested on two model drugs, isradipine (ISR) and chlorpheniramine (CPA) which are respectively practically insoluble and freely soluble. Results show that, regardless of the drug properties which do not significantly affect the drug delivery, the release kinetics is mainly controlled by four factors, (i) the PEG proportion in the membrane, (ii) the tablet surface area, (iii) the osmotic agent proportion and (iv) the drug layer polymer grade. The influence of each key formulation factors on the release mechanism was investigated defining their applicability range. A mathematical approach was developed to predict the drug delivery kinetics varying the PPOP controlling factors and helps to more efficiently design PPOP.

Terahertz pulsed imaging, a novel process analytical tool to investigate the coating characteristics of push–pull osmotic systems

The aim of this study was to investigate coating characteristics of push-pull osmotic systems (PPOS) using three-dimensional terahertz pulsed imaging (3D-TPI) and to detect physical alterations potentially impacting the drug release. The terahertz time-domain reflection signal was used to obtain information on both the spatial distribution of the coating thickness and the coating internal physical mapping. The results showed that (i) the thickness distribution of PPOS coating can be non-destructively analysed using 3D-TPI and (ii) internal physical alterations impacting the drug release kinetics were detectable by using the terahertz time-domain signal. Based on the results, the potential benefits of implementing 3D-TPI as quality control analytical tool were discussed.

Statistical Evaluation of Stability Data of Pharmaceutical Products for Specification Setting

AbstractRecent experience has shown that the regulatory authorities try to narrow specifications for a new drug product closely around stability data that have been generated in the course of registration stability testing. This should ensure that the quality of the marketed product is produced within tight limits, very similar to the quality which is registered. A strategy is proposed to set scientifically based, statistically justified specifications. The long-term stability data available at the time point of registration application are extrapolated to a target shelf life (usually 36 months) of the new pharmaceutical product by linear regression. Batch-to-batch heterogeneity is tested as prescribed by the International Conference on Harmonization (ICH) guideline on stability testing of new drug substances and drug products. The data of different batches are combined in appropriate statistical models for further evaluation. The one-sided 99% confidence limit for individuals is used for the determinatio...

Evaluation of the Tablet Core Factors Influencing the Release Kinetics and the Loadability of Push–Pull Osmotic Systems

Push–pull osmotic systems have been developed to deliver poorly soluble drugs in a modified-release fashion. The aim of this study was to investigate the influence of the tablet core factors on the drug release kinetics and loadability. The release kinetics was efficiently modulated by varying either the proportion of osmotic agent or the drug layer polymer grade as an alternative to change the membrane characteristics. High osmotic agent proportions and viscous-grade polymers were recommended to formulate high drug loads up to 20% without losing both the release completeness and the zero-order drug release kinetics.