(1048) Preparation and Stability of Compounded Capsules Containing Amlodipine and Hydrochlorothiazide Titration Tablets for the Treatment of Hypertension

Objectives: The objective of this study is to provide a validated method for preparing amlodipine-HCTZ capsules in different dose combinations in a compounding setting using Resonant Acoustic Mixing (RAM) technology to create titration tablets. This technology combines acoustic and mechanical energy in the mixing process which results in an effective blend mixing requiring low mixing times which is advantageous in compounding. Amlodipine is a calcium channel blocker used for the treatment of hypertension as monotherapy or in combination with other drugs including thiazide diuretics such as hydrochlorothiazide (HCTZ). Currently, the combination of these two drugs in one same tablet or capsule is not commercially available in the U.S., which represents an opportunity for compounding pharmacies to improve adherence among individuals with multiple drug regimens.

Methods: Blends of Amlodipine and Hydrochlorothiazide with Prosolv Easytab, were mixed separately in a RAM at high intensity for two minutes. The blends were compressed separately in a bench-top tablet press (TDP-0) into tiny tablets, small enough to fit in a capsule size 1.
The titration tablets contained 5mg of Amlodipine and 12.5 of Hydrochlorothiazide. The final capsule dose was adjusted by adding the selected number of titration tablets in the capsules. A total of four dose combinations of Amlo-HCTZ capsules were prepared as follows: AMLO/HCTZ (5mg/25 mg), AMLO/HCTZ (10mg/12.5 mg), AMLO/HCTZ (10mg/25 mg), and AMLO/HCTZ (10mg/50 mg). The tablets were encapsulated using a manual encapsulation machine (Profiller 1100) into size 1 capsules.
Capsules samples from each batch (n=6) were tested for content uniformity, drug potency and stability at time zero and one month using HPLC Analysis. Dissolution testing of the titration tablets and filled capsules was conducted following the USP monographs for each drug.

Results: All samples met content uniformity, potency and stability requirements at zero and one-month intervals. Dissolution testing of tablets and capsules met USP criteria of NLT 75% in 30 minutes using USP Apparatus II for amlodipine, and NLT 60% in 45 minutes using USP apparatus I for HCTZ. The tablets and the filled capsules met key quality attributes, including one month stability. ANOVA analysis showed no statistical difference between time zero and 1 month in all cases (p > 0.05).

Conclusions: Resonant acoustic mixing technology is a suitable method to compound different amlodipine and hydrochlorothiazide combinations in capsules using titration tablets. This method enables the pharmacist to prepare different drug combinations in a capsule in a non-interacting manner at the formulation stage since the APIs are not in direct contact in the dosage form.