Determining Abuse Deterrence Performance of Poly (ethylene oxide) Using a Factorial Design

Purpose: The purpose of this study was to determine the effects of thermal processing and antioxidant formulation variables on the abuse deterrence performance of a high molecular weight poly(ethylene oxide) (PEO) polymer. Methods: A 24 factorial design with one categorical factor (antioxidant type) and three continuous factors (curing time, curing temperature, % antioxidant) was used. Abuse deterrence performance was evaluated using solution viscosity, surface melting temperature, and mechanical strength. Thermal degradation of PEO powders before compaction was also studied using DSC, FTIR spectroscopy, and viscosity analysis. Results: Our results showed that curing temperature and type of antioxidant can significantly affect the deterrence performance of PEO. The main effect plot for viscosity shows the most prominent factors affecting viscosity are curing temperature and type of antioxidant. However, curvature in the linear model obtained was not sufficient to completely describe the behavior. For surface melting temperature, butylated hydroxytoluene was associated with higher surface melting temperatures compared to ascorbic acid. Additionally, higher percent of antioxidant resulted in higher melting temperature. Particle size distribution to indicate mechanical strength showed no significant effects of tested factors. This suggests that comminution method has more prominent effect on tablet fragment size than the formulation and processing factors studied. Conclusion: While heat confers the mechanical strength to the polymer, it can diminish its physical stability and solution state viscosity. The experimental studies showed that prolonged exposure to high temperatures, even in the presence of antioxidants, can severely hamper polymer deterrence performance in both solid and solution states

Novel Expandable Platforms for Gastric Retention

Extending the residence time of the drugs with low absorption window is a holy grail in oral drug delivery. If such drug passes the absorption segment, it will be wasted away with no further absorption throughout the gastrointestinal tract. Harsh stomach environment, diet status (fed or fasted), subject to subject variability, stomach motility, dynamic change of the stomach pH, food effect and more are all accounted for a gastric retention program to be very challenging. Although a few concepts including floating, mucoadhesion, swelling and expansion have been utilized in designing gastric retention (GR) platforms, no technology has so far proved to be commercially feasible and therapeutically effective in enhancing the absorption and bio-availability of the drugs with low absorption window. To be effective, a GR platform is expected to stay in the stomach preferably in a fasted state for 6-8 hrs, to release its embedded drug in a controlled manner and finally to disintegrate for a safe removal from the body. Overall, a potential gastric retention platform should generally meet requirements such as pharmaceutical acceptability, mechanical properties, ease of processing and disintegrability. In this project, two novel approaches will be examined to achieve gastric retention. First, a strong platform based on a cryogeling polymer, poly (vinyl alcohol) (PVOH) will be prepared via a freezing-thawing process. Certain factors will be optimized to balance between the platform properties and further processing needs. To make the platform disintegrable, two methods will be used; imprinting weak areas and including extractable particles into the platform base. The platforms will be eventually characterized by mechanical and disintegration (erosion) properties which will be determining their gastric retention potential. Due to its novel nature, the project has a great potential to be patented and licensed to the pharmaceutical industries for further development

Routes of Opioid Abuse and its Novel Deterrent Formulations

This review aimed to investigate the abuse patterns of common prescription opioids currently on the market by collecting large-scale surveys of different abuser populations. Furthermore, we aimed to analyze the efficacy and properties of currently implemented abuse-deterrent formulations (ADF) for these compounds. Our investigation showed that while oxycodone and oxymorphone are primarily abused by oral ingestion and insufflations, respectively, their ADF products (reformulated OxyContin and Opana ER) show some encouraging results to deter their abuse. Tapentadol is not popular amongst abuser populations, its ADF are difficult to tamper with, and it does not produce significantly desirable effects in noncompliant patients when compared to other opioids. Hydromorphone is predominantly abused by injection, and any effective abuse-deterrent strategy must specifically prioritize and target this route. Current formulations have successfully conferred aversive properties onto the drug in the event of preparation for injection, yet overall rates of hydromorphone abuse remain high, suggesting that more innovative steps need to be taken. Despite novel deterrent technologies that collectively offer deterrence by insufflations, injection and co-ingestion with alcohol, more priority needs to be given to deterring the most common and accessible route of abuse, i.e., oral ingestion of multiple doses

FREE AND LOADED SWELLING OF SUPERDISINTEGRANTS

Objective. The objective of this study was to study the behavior of superdisintegrants under free and loaded conditions. Background. Superdisintegrants are characterized by their swelling ratio, which determines their capacity to disintegrate tablets. Swelling ratio is determined by weight or volume of the dry versus swollen sample. While high swelling capacity and slow swelling rate can be successfully measured by weight or volume changes, a high standard deviation is expected when swelling is negligible or very fast. Moreover, the swelling capacity and rate can be changed when isolated particles of the superdisintegrant are dispersed in the swelling medium (free swelling) or compressed into a tablet before exposed to the swelling medium (loaded swelling). We therefore developed a new effective method to measure the swelling pressure of superdisintegrants. Methods. Tablets of three different superdisintegrants were prepared with same hardness and weight. Swelling pressure was determined by the novel probe attached to the Brookfield CT3 texture analyzer; weight selling ratio of the superdisintegrants as particle and tablet was also measured. Results. Under free swelling, Explotab displayed the maximum swelling capacity, while maximum swelling pressure was obtained for Croscarmellose. We also found most water absorbed by explotab was interstitial, while it was bulk absorption for Croscarmellose. Polyplasdone showed almost same free and loaded swelling, the swelling was low and fast, which can be accounted for by its wicking action. Conclusion. Although useful for comparative studies, the free swelling data cannot be used to characterize disintegration power of superdisintegrants in tablets. Grants. N

The Effect of Polymer Type and Molecular Weight on Mechanical Properties of Oral Films

Objective:Investigate mechanical attributes of oral films composed of common pharmaceutical polymers affecting their manufacturing. Background:Oral is the preferred route of drug administration for its safety and patient compliance. Oral films are relatively new dosage forms with the potentials of replacing tablets and capsules for their ease of production and administration. However, the formulation of oral films is challenging as the selection of the appropriate drug carrier can influence the performance of dosage forms to a great degree. Therefore, selecting the right carrier with adequate mechanical properties is the first step in designing such dosage forms. Methods:Oral films of sodium carboxymethylcellulose (CMC) and chitosan at different molecular weights (MW) were prepared by the solvent casting method (1% film solution dried at 40°C, 24 hr). Rupture test was performed on the samples using a Texture Analyzer (CT3-4500) equipped with TA33 probe. Puncture strength (PS) and elongation at break (EB) were calculated for all samples. All measurements were performed in triplicates. Results:Chitosan films showed higher PS and EB% values than CMC films at different molecular weights indicating that chitosan films are stronger and more flexible. Compared to commercial oral films, both CMC and chitosan films showed higher PS and EB%. Moreover, the mechanical properties of CMC films were affected by MW (p-value Conclusion:Mechanical properties of oral films can be tuned and adjusted using different polymers and polymers possessing different molecular weights. Grants:This study was supported by NSU Grant 335114