PREVENTION OF ACTIVE DRUG EXTRACTION USING ABSORBENT CLAY COMPOSITE
Abstract
Objective. To determine the affinity (entrapment efficiency) of bentonite to capture and entrap pharmaceutical actives in aqueous drug solutions. Background. Bentonite and other montmorillonites have large ion exchange capacities, and historically been used for oral detoxification. The main advantage of bentonite is its ability to entrap cationic drugs and swell to several times its own weight in water. These properties are useful in formulating abuse deterrent medications resistant to methods used for intravenous injection. Methods. Acetaminophen, diclofenac sodium, dextromethorphan hydrobromide, lidocaine hydrochloride, and verapamil hydrochloride were selected to represent different classes of amphoteric, anionic, and cationic structures. Drug solutions at low (200 μg/mL) and high (1000 μg/mL) concentrations were prepared for liquid state drug complexation and entrapment. In glass vials, increasing amounts of bentonite (25, 50 and 100 mg) were mixed with 10 mL of drug solution and vortexed for 5 seconds. After standing for 1 minute, the mixtures were centrifuged (1500 rpm) for 5 minutes to separate the swollen bentonite from free liquid. The supernatant was then filtered and measured for drug concentration using UV-Vis spectroscopy at corresponding drug wavelengths of 248, 275, 276, 263, and 278 nm, respectively. Results. Bentonite used in this study did not selectively bind to acetaminophen (non-ionic) or diclofenac sodium (anionic), whereas it selectively bound to all three cationic drugs with more than 80% binding capacity. Conclusion. By forming stable complexes with cationic drugs, bentonite clays can effectively be used in formulations of abuse-deterrent medications to prevent abuse by injection and possibly nasal insufflation. Grants. #PFRDG 335357
PREVENTION OF ACTIVE DRUG EXTRACTION USING ABSORBENT CLAY COMPOSITE
POSTER PRESENTATIONS
Objective. To determine the affinity (entrapment efficiency) of bentonite to capture and entrap pharmaceutical actives in aqueous drug solutions. Background. Bentonite and other montmorillonites have large ion exchange capacities, and historically been used for oral detoxification. The main advantage of bentonite is its ability to entrap cationic drugs and swell to several times its own weight in water. These properties are useful in formulating abuse deterrent medications resistant to methods used for intravenous injection. Methods. Acetaminophen, diclofenac sodium, dextromethorphan hydrobromide, lidocaine hydrochloride, and verapamil hydrochloride were selected to represent different classes of amphoteric, anionic, and cationic structures. Drug solutions at low (200 μg/mL) and high (1000 μg/mL) concentrations were prepared for liquid state drug complexation and entrapment. In glass vials, increasing amounts of bentonite (25, 50 and 100 mg) were mixed with 10 mL of drug solution and vortexed for 5 seconds. After standing for 1 minute, the mixtures were centrifuged (1500 rpm) for 5 minutes to separate the swollen bentonite from free liquid. The supernatant was then filtered and measured for drug concentration using UV-Vis spectroscopy at corresponding drug wavelengths of 248, 275, 276, 263, and 278 nm, respectively. Results. Bentonite used in this study did not selectively bind to acetaminophen (non-ionic) or diclofenac sodium (anionic), whereas it selectively bound to all three cationic drugs with more than 80% binding capacity. Conclusion. By forming stable complexes with cationic drugs, bentonite clays can effectively be used in formulations of abuse-deterrent medications to prevent abuse by injection and possibly nasal insufflation. Grants. #PFRDG 335357