Assessing Abuse-Deterrent formulations utilizing Ion-Exchange resin complexation processed via Twin-Screw granulation for improved safety and effectiveness.

Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist-antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.

Studies on the in vitro ion exchange kinetics and thermodynamics and in vivo pharmacokinetics of the carbinoxamine-resin complex.

The short half-life and bitter taste of carbinoxamine maleate2 (CAM) lead to poor compliance by pediatric patients who are being treated for allergic rhinitis. To address these issues, carbinoxamine-resin complexes3 (CRCs) were prepared by ion exchange and then coated with Kollicoat SR 30D. The resultant microencapsulated carbinoxamine-resin complexes4 (MCRCs) were dispersed into the medium to obtain the final suspensions. The drug loading kinetics and thermodynamics of CRCs, anti-swelling mechanism of the impregnant in MCRCs, in vitro release, and in vivo pharmacokinetics of the suspensions were systematically evaluated. The drug loading process was found to obey a first-order kinetic process that was spontaneous, entropy-reduced and exothermic, and the diffusion of CAM into the resin was the rate-limiting step. During microencapsulation, the impregnant could create a certain buffer space to control the swelling of CRCs and maintain the coating film intact. The homemade preparations had release behaviors similar to that of the reference in vitro and achieved sustained release in vivo. The low drug loading preparation had a higher relative bioavailability of 109% owing to its faster release and better dispersibility. Therefore, the suspensions based on MCRCs could be successfully applied to treating allergic rhinitis in children.

Formulation and evaluation of taste masked mouth dissolving tablets of levocetirizine hydrochloride.

Aim of this research work was to develop mouth dissolving tablet that disintegrates rapidly in mouth by using tasteless complex of Levocetirizine and Tulsion-335. Effect of different parameters such as swelling time, resin activation, drug resin ratio as well as stirring time was optimized by taste and percentage drug loading. Formulated DRC (Drug Resin Complex) was characterized by infrared spectroscopy, thermal analysis and X-ray diffraction pattern. Tablets were formulated by wet granulation with PVP as binder, Sodium Starch Glycolate (SSG) and Crospovidone as super disintegrants. In these batches optimum hardness was achieved but disintegration time was found to be very high as ≥ 70 second, so further trials were planned by using different superdisintegrants such as Croscarmellose sodium, Sodium Starch Glycolate (SSG) as well as Crospovidone by wet granulation method. Tablets formulated with 7.5% crospovidone showed comparatively low disintegration time (25 sec), wetting time (20 sec) and friability (0.60 %) than the other batches. In present study we optimized the conditions required for maximum drug loading of Levocetirizine with Tulsion-335. Among different superdisintergants, crospovidone was found suitable with drug-resin complex to get the low disintegration time, wetting time and friability of tablets.