(1049) Preparation and Stability of Doxycycline Hyclate Capsules Using Resonance Acoustic Mixing Technology

Objectives: The objective of this study is to develop a validated method for preparing high quality compounded capsules of doxycycline hyclate (DOX), using Resonance Acoustic Mixing Technology (RAM) to blend the powder formulation. Doxycycline is a broad-spectrum antibiotic with activity against gram-positive and gram-negative pathogens. It is commonly used as a first line treatment for some respiratory tract, genitourinary, skin, and soft tissue infections among others. Being a commonly used antibiotic, the occurrence of a doxycycline shortage may present a challenge to the healthcare system, but an opportunity for compounding pharmacies.

Methods: Three formulations of DOX 100 mg capsules were prepared with three different excipients widely used in pharmacy. Two were co-excipients of silicified microcrystalline cellulose (Si-MCC) confectioned for direct drug-blending use and the third one was lactose monohydrate (compounding grade).
Blends of 20 grams were prepared in the RAM using the highest intensity setting for 60 seconds in a polypropylene container. The drug loads were adjusted for each formulation to maintain capsule size constant. Fifty capsules size # 1 of each formulation were filled using a ProFiller 1100 with a target fill weight necessary to achieve 100 mg. of DOX per capsule. Pure DOX capsules (used as control) and the DOX experimental capsules were analyzed for content uniformity of drug, potency, dissolution, and stability at time zero, 1 month and 6 months using a validated HPLC assay.

Results: The formulations of the two co-excipients of MCC fully met all the acceptance criteria for content uniformity, potency, chemical stability including the USP criteria for dissolution. The lactose-based formulation did not pass the content uniformity tests and was discarded for stability testing.

Conclusions: Our findings demonstrated that RAM technology can be safely used to compound DOX capsules with the two Si-MCC co-excipients. The selection of excipient and the proper mixing conditions are key elements for using RAM technology successfully in compounding.