(527b) Formulation Design Evaluation for a Single Layer Osmotic Capsule

A single layer osmotic capsule for controlled-release has been examined to provide an easy to manufacture capsule analog to single layer osmotic tablet delivery systems.   The impact of the single layer capsule core contents on dissolution performance was evaluated.  Factors included: 1) drug type and level – acetaminophen (high solubility), caffeine (high solubility), and carbamazepine (low solubility); 2) grade, particle size, and level of the viscosifying polymer (hydroxyethylcellulose); 3) type and level of binder (copovidone and hydroxypropylcellulose); 4) solid fraction of the capsule cores; and 5) type and level of the osmogen (sorbitol and sodium chloride).  Single layer capsule cores containing various amounts of the preceding materials were encapsulated in a semi-permeable osmotic capsule shell comprised of 60% cellulose acetate and 40% PEG 3350.  Screening studies were performed to evaluate the impact of hydroxyethylcellulose viscosity and particle size, binder type, capsule core solid fraction, and drug solubility on the lag time and the initial, linear release rate from the osmotic capsule.  The  screening studies indicated that drug solubility had an impact on the lag time and the initial, linear release rate, while the other factors showed minimal impact on the drug release from the single layer osmotic capsule.  A subsequent statistical design of experiments (DOE) study examined the formulation space for the single layer osmotic capsule using acetaminophen.  The DOE study indicated that formulation changes to the single layer core could result in T₅₀ (time until 50% of the drug is dissolved) values ranging from 5 hours to greater than 24 hours.  Further, drug was released faster from capsules with higher osmogen to drug loading ratios.  For lower osmogen to drug loading ratios, the amount of hydroxyethylcellulose and the ratio of sorbitol to sodium chloride had a significant effect on the rate of release from the osmotic capsule, with higher levels of sodium chloride and hydroxyethylcellulose increasing the release rate.  In summary, the design of the single layer capsule core formulation can provide a drug product formulator with a broad range of flexibility in order to achieve varying release rates from an osmotic capsule.