Oxycodone hydrochloride immediate-release analgesic for managing severe pain: abuse-deterrent formulations

AH Kibbe,1 TS Franko,2 VM Shah2 1Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, USA; 2Department of Clinical Pharmacy, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, USA Abstract: This paper is an expert opinion in response to the development of abuse-deterrent immediate-release tablets containing oxycodone HCl. There is a potential impact, both positive and negative, of this type of dosage form on patients, those suffering from the disease of addiction, health care providers, and the cost of health care. Keywords: non-metabolizable polymer, opioids, risk/benefit, IV abuse, nasal abus

Effect of starting material particle size on its agglomeration behavior in high shear wet granulation

The effect of anhydrous lactose particle size distribution on its performance in the wet granulation process was evaluated. Three grades of anhydrous lactose were used in the study: “as is” manufacturer grade and 2 particle size fractions obtained by screening of the 60M lactose. Particle growth behavior of the 3 lactose grades was evaluated in a high shear mixer. Compactibility and porosity of the resulting granules were also evaluated. A uniaxial compression test on moist agglomerates of the 3 lactose grades was performed in an attempt to explain the mechanism of particle size effect observed in the high shear mixer. Particle growth of anhydrous lactose in the high shear mixer was inversely related to the particle size of the starting material. In addition, granulation manufactured using the grade with the smallest particle size was more porous and demonstrated enhanced compactibility compared with the other grades. Compacts with similar porosity and low liquid saturation demonstrated brittle behavior and their breakage strength was inversely related to lactose particle size in the uniaxial compression test, suggesting that material with smaller particle size may exhibit more pronounced nucleation behavior during wet granulation. On the other hand, compacts prepared at higher liquid saturation and similar compression force exhibited more plastic behavior and showed lower yield stress for the grade with smallest particle size. The lower yield stress of compacts prepared with this grade may indicate a higher coalescence tendency for its granules during wet granulation

Method to recover a lipophilic drug from hydroxypropyl methylcellulose matrix tablets

A reverse-phase high-performance liquid chromatographic (HPLC) method for recovery of the lipophilic drug, alprazolam, from matrix tablets containing the hydrophilic polymer hydroxypropyl methylcellulose (HPMC) was developed. Lipophilic drugs, such as alprazolam, are difficult to completely extract and quantitate from tablets containing HPMC polymer. The percentage of recoveries of alprazolam from placebo powder spiked with alprazolam stock solution and from placebo powder mixed with alprazolam powder were about 100% and 85% to 95%, respectively. The validated method using water to completely dissolve HPMC before the addition of a strong solvent to dissolve and extract the drug from the HPMC solution was shown to be the most reproducible method. Different molecular weight distributions of the HPMC polymer, such as HPMC-K4M and HPMC-K100LV, did not influence the dissolution results of alprazolam using this validated method. Similarly, the excipients composing the matrix tablet formulations, such as dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium sulfate dihydrate, sucrose, dextrose, and lactose monohydrate, did not influence the percent recovery of alprazolam. The recovery method reported herein was shown to be the most efficient to achieve complete recovery of alprazolam from powder blends and tablets containing a variety of excipients and different grades of HPMC

In vitro test to evaluate the interaction between synthetic cervical mucus and vaginal formulations

The interaction and mixing between a bilayer sample of mucus and vaginal formulation was evaluated through viscosity measurements with respect to time and shear. Physical mixtures of mucus and vaginal formulation were used as controls. Three test protocols were designed: (1) constant shear, (2) intermittent shear, and (3) delayed shear. Several marketed vaginal products (Gynol II, KY Plus, KY, and Advantage-S) and experimental formulations (C31G with hydroxyethylcellulose [HEC]) were evaluated and compared by these tests. The results of the constant shear test showed that the shear stress profile of the bilayer approached that of the corresponding physical mixture, consistent with complete mixing of the bilayer under shear. The time taken for the bilayer to mix completely was in the following order: KY Plus > Gynol II and C31G > KY > Advantage-S. Under the intermittent shear protocol, the following order for complete mixing was observed: KY Plus > C31G > Gynol II > KY > Advantage-S. The 2 products evaluated by the delayed shear test, C31G and Gynol II, were both completely mixed at 180 minutes. The development of an in vitro test, when coupled with in vivo data, should serve in the screening and evaluation of future vaginal formulations