Amoxicillin, doxycycline, and clindamycin are not only important in treatment of numerous infections, but also valuable medical countermeasures during public health emergencies. (LeCorn et al., 2007, Hutchings et al., 2019, Adedeji, 2016, Huemer et al., 2020, Aminov, 2009) The Strategic National Stockpile (SNS) is a national repository of medical countermeasures that includes pharmaceutical (e.g., antibiotics, biologics, vaccines, antitoxins) and nonpharmaceutical products that could be used to supplement and resupply state, local, tribal, and territorial jurisdictions during large-scale biological, chemical, radiological, or nuclear incidents; natural disasters; or public health emergencies related to emerging infectious diseases. Managed by the Administration for Strategic Preparedness and Response (ASPR) under U.S. Department of Health and Human Services (HHS), stockpiles of amoxicillin, doxycycline, and clindamycin are maintained for potential use during public health emergencies caused by bacterial infections. The stockpiled antibiotics are typically in solid oral dosage forms not specially designed for pediatric patients and may also not be suitable for adult patients with difficulties swallowing. During an emergency, the need for pediatric-specific formulations may exceed quantities of commercially available and stockpiled liquid or powder for oral suspension formulations. Care providers often need to conduct extemporaneous dose preparation from solid oral dosage forms (i.e., capsules, tablets) to provide prescribed doses mixed with food or liquids to pediatric patients and adult patients unable to swallow capsules or tablets. (Use of Liquids, 2018).

In case of solid oral dosage forms, common manipulation of dosage form is to open and split capsule contents or crush tablets, and the manipulated dosage forms can be further mixed with vehicles such as liquid and soft foods to deliver the specific dose and to improve the taste of the administered drug. (Freerks et al., 2022, Batchelor et al., 2018) However, different types of liquid and soft foods differ significantly in their taste, content, and physicochemical properties, and even the same type of food can be different from different manufacturers. These differences in food matrices can further affect the drug solubility and dissolution rate and can also affect the stability and in vivo performance of the drug products. There are a large variety of liquid and soft liquid foods that could potentially be used as dosing vehicles. (Batchelor et al., 2018, Chun et al., 2000) Furthermore, the preparation process, for example, mixing times and tools of the food-drug mixtures can also be important to produce homogeneous mixtures for dosing accuracy. (Wollmer et al., 2022) To address these knowledge gaps in the understanding of the effects of foods and drinks on the availability, stability, and dose accuracy of the drugs, and to standardizing the selection and qualification of food vehicles to be mixed with the drug product and preparation and use instructions for food-drug mixtures, the FDA initiated a draft guidance “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments”. (Use of Liquids, 2018, Freerks et al., 2022) The guidance recommends that a soft or liquid food can be used as a vehicle only when there is no significant impact on product quality including potency, in vitro dissolution, and stability.

In the current study, we selected 16 foods to evaluate the potential impact on product quality of food-drug interactions with capsule formulations of amoxicillin trihydrate (TH), doxycycline hyclate (H), and clindamycin hydrochloride (HCl) to determine whether a proposed food vehicle is compatible and suitable for use with the drug products. Specifically, potency and content uniformity of intact capsules was tested, while dissolution and stability of capsules were tested on the mixtures of capsule content and food. Homogeneity of drug-food mixture was assessed in various utensils and by varying mixing times for all drug-food mixtures.