The Impact of Heat on Mechanical and Drug Release Properties of Tablets Containing Low Molecular Weight PEO

Objective. Evaluate crush resistance ability of LMW PEO that is further improved when the products containing PEO are thermally processed. Background. PEO may be used in abuse deterrent formulations (ADFs) to decrease opioid abuse by preventing physical tampering. Methods. Tablets prepared using 200 mg LMW PEO, 275 mg Avicel, and 25 mg dextromethorphan HCl. The mechanical strength of the tablets was determined using a ball-mill grinder. Tablets (control and heated) were placed in the mill and subjected to steel balls revolving at full speed at a frequency of 25 Hz for 5 min. Particles were then sieved to determine particle size distribution via sieve analysis. Furthermore, the dissolution study of both control and heat-treated tablets was carried out in 0.1% HCl dissolution medium. Results.As it was previously mentioned, the more particles smaller than 500 μm, the less crush resistant tablets are. In control tablets 61.86±11.4% of particles are smaller than 500 μm and this amount decreased to 5.24±5.66 in cured tablets at 80°C (P Conclusion. Tablets containing LMW PEO can offer significant mechanical resistance and tunable drug release if heated at temperatures above the melting point and well below the degradation temperature of the polymer

The Impact of Heat on Mechanical and Drug Release Properties of Tablets Containing Low Molecular Weight PEO (LMW PEO)

Objective. Evaluate crush resistance ability of LMW PEO that is further improved when the products containing PEO are thermally processed. Background. PEO may be used in abuse deterrent formulations (ADFs) to decrease opioid abuse by preventing physical tampering. Methods. Tablets prepared using 200 mg LMW PEO, 275 mg Avicel, and 25 mg dextromethorphan HCl. The mechanical strength of the tablets was determined using a ball-mill grinder. Tablets (control and heated) were placed in the mill and subjected to steel balls revolving at full speed at a frequency of 25 Hz for 5 min. Particles were then sieved to determine particle size distribution via sieve analysis. Furthermore, the dissolution study of both control and heat-treated tablets was carried out in 0.1% HCl dissolution medium. Results.As it was previously mentioned, the more particles smaller than 500 μm, the less crush resistant tablets are. In control tablets 61.86±11.4% of particles are smaller than 500 μm and this amount decreased to 5.24±5.66 in cured tablets at 80°C (P Conclusion. Tablets containing LMW PEO can offer significant mechanical resistance and tunable drug release if heated at temperatures above the melting point and well below the degradation temperature of the polymer

Deterrent Properties of Thermally-Manipulated High Molecular Weight Poly(ethylene oxide) ( HMW PEO)

Objective. In this study, we aimed to manipulate the pure HMW PEO and the tablets containing HMW PEO to evaluate the structural and functional properties of the PEO and the PEO tablets under abuse conditions. Background. In Abuse deterrent formulations (ADFs), the HMW PEO offers extraction resistance properties. They have the potential to decrease opioid abuse by preventing chemical (e.g., drug extraction) tampering. Methods. HMW PEO powder (Sentry™ Polyox™ WSR-301, Mw 4,000,000 Da) was spread over a glass plate, and heated in an air-circulated oven at 180°C for 1 hr. A single station compression press tableting machine was used to prepare tablets (200 mg HMW PEO and 300 mg Avicel) using a direct compression method. The tablets were also heated in an air-circulated oven at 180°C for 1 hr. The dissolution study of tablets was done in 0.1% HCl at 25°C. Results. The FTIR spectra of the HMW PEO powder treated at 180°C indicated an oxidative degradation at 1720 cm -1. The rheological behavior including viscosity and yield stress of the PEO solutions confirmed a pseudoplastic flow behavior for the controlled solution of HMW PEO, whereas the heat-treated sample showed almost no viscosity when manipulated at 180°C. The dissolution study of cured tablet showed that 36.34±10.28% of drug was released after 1 hr; whereas, 19.19±2.13% of drug was in dissolution medium containing control tablet. This confirms that the oxidized PEO backbone (Due to heat-treating to 180°C) releases the drug faster than PEO chains backbone. Conclusion. HMW PEO is extremely sensitive to thermal manipulations. If the dosage forms containing this polymer are thermally manipulated at temperatures as high as its degradation temperature, almost all deterrent features of this polymer will be lost as evidenced by dramatic changes in its structure and flow behavior

Cytotoxicity of Thermally Manipulated Ethylene Oxide Polymers Used in Abuse Deterrent Formulations

Objective. Evaluate human Gingiva derived stem cells (GMSCs) and Osteoblasts like cells (MG63) cells viability on heat-treated high and low molecular weight PEO films. Background. Features like low toxicity, lack of immunogenicity, antigenicity and excellent biocompatibility of PEO make it a preferred polymer in abuse deterrent formulations. However, PEO properties can change at higher temperature of abuse leading to oxidation and potential toxicity that is studied here. Methods. LMW (10% solution) and HMW (2% solution) PEO films were prepared by casting their solutions in glass petri-dish. The cells cultured on to a flat bottom 24 well plate with a density at 1X 105 were exposed to 60 mg/mL of sterilized PEO samples and allowed to incubate for 24 hours in 37°C. The cytotoxic effect of the PEO was assessed and the viability of the cells was determined by using the commercially available Live/Dead assay kit (Molecular probes Invitrogen detection technologies, Carlsbad, CA) Results. Cell viability in the presence of HMW 180°C and HMW 80°C films were compared with PEO control. The cell viability of both GMSCs and MG63 significantly reduced in HMW 180°C, while the cell viability in HMW 80°C was comparable to HMW control, Conclusion. Regardless of its molecular weight, PEO can become cytotoxic when heated at above 80°C. This is particularly important as abuse-deterrent tablets containing PEO are generally heated at high temperatures in order to abuse by injection and insufflation

Cytotoxicity of Thermally Manipulated Ethylene Oxide Polymers Used in Abuse Deterrent Formulations

Objective. Evaluate human Gingiva derived stem cells (GMSCs) and Osteoblasts like cells (MG63) cells viability on heat-treated high and low molecular weight PEO films. Background. Features like low toxicity, lack of immunogenicity, antigenicity and excellent biocompatibility of PEO make it a preferred polymer in abuse deterrent formulations. However, PEO properties can change at higher temperature of abuse leading to oxidation and potential toxicity that is studied here. Methods. LMW (10% solution) and HMW (2% solution) PEO films were prepared by casting their solutions in glass petri-dish. The cells cultured on to a flat bottom 24 well plate with a density at 1X 105 were exposed to 60 mg/mL of sterilized PEO samples and allowed to incubate for 24 hours in 37°C. The cytotoxic effect of the PEO was assessed and the viability of the cells was determined by using the commercially available Live/Dead assay kit (Molecular probes Invitrogen detection technologies, Carlsbad, CA) Results. Cell viability in the presence of HMW 180°C and HMW 80°C films were compared with PEO control. The cell viability of both GMSCs and MG63 significantly reduced in HMW 180°C, while the cell viability in HMW 80°C was comparable to HMW control, Conclusion. Regardless of its molecular weight, PEO can become cytotoxic when heated at above 80°C. This is particularly important as abuse-deterrent tablets containing PEO are generally heated at high temperatures in order to abuse by injection and insufflation

Bioinspired Polymers: Transformative Applications in Biomedicine and Regenerative Medicine.

Bioinspired polymers have emerged as a promising field in biomaterials research, offering innovative solutions for various applications in biomedical engineering. This manuscript provides an overview of the advancements and potential of bioinspired polymers in tissue engineering, regenerative medicine, and biomedicine. The manuscript discusses their role in enhancing mechanical properties, mimicking the extracellular matrix, incorporating hydrophobic particles for self-healing abilities, and improving stability. Additionally, it explores their applications in antibacterial properties, optical and sensing applications, cancer therapy, and wound healing. The manuscript emphasizes the significance of bioinspired polymers in expanding biomedical applications, addressing healthcare challenges, and improving outcomes. By highlighting these achievements, this manuscript highlights the transformative impact of bioinspired polymers in biomedical engineering and sets the stage for further research and development in the field

Cryogels: Advancing Biomaterials for Transformative Biomedical Applications.

Cryogels, composed of synthetic and natural materials, have emerged as versatile biomaterials with applications in tissue engineering, controlled drug delivery, regenerative medicine, and therapeutics. However, optimizing cryogel properties, such as mechanical strength and release profiles, remains challenging. To advance the field, researchers are exploring advanced manufacturing techniques, biomimetic design, and addressing long-term stability. Combination therapies and drug delivery systems using cryogels show promise. In vivo evaluation and clinical trials are crucial for safety and efficacy. Overcoming practical challenges, including scalability, structural integrity, mass transfer constraints, biocompatibility, seamless integration, and cost-effectiveness, is essential. By addressing these challenges, cryogels can transform biomedical applications with innovative biomaterials

Sunflower Oil-Based Polyol-Urethane Nanoparticles for Sustained Delivery of Olanzapine

Objective. A facile route based on cyclic carbonate ring-opening reaction has been utilized to synthesize a bio-based polyol-containing urethane bond [polyol-urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. Background. The forefront horizon of biomedical investigations in recent decades is parceling-up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green-based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. Methods. The biodegradable and biocompatible hyper-branched POU containing several hydroxyl and urethane bonds, was synthesized via an easy method of cyclic carbonate ring opening reaction followed by ethanol amine addition. After characterization, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. Results. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behavior (82 ± 3% after 168 h), by the Higuchi-based release mechanism. Pharmacokinetics assessments of POU-olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. Conclusion. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods. The POU is a safe drug carrier due to bio-based materials used in its preparation