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The majority of all newly identified active pharmaceutical ingredients (APIs) have a low solubility in water (partly smaller than marble). In order to enhance their solubility and bioavailability, the formulation of these APIs as part of therapeutic deep-eutectic systems (THEDES), has been recently shown to be a promising approach. By choosing the right excipient, the melting point of the API/excipient mixture can be lowered below body temperature or even room temperature, resulting in a liquid formulation. To date, due to a lack of mechanistic understanding of how THEDES are formed, the identification of suitable excipients for a given API is almost exclusively based on heuristic decisions and trial-and-error based approaches. This is both very time-consuming and expensive. The purpose of this work is to reduce the experimental effort to identify suitable excipients for a given API solely based on the melting properties (melting temperature and melting enthalpy) of API and excipient and accounting for intermolecular interactions via a predictive thermodynamic model (in this case UNIFAC(Do)). Lidocaine, ibuprofen and phenylacetic acid were considered as model APIs, whereas thymol, vanillin, lauric acid, para-toluic acid, benzoic acid, and cinnamic acid were considered as model excipients. The formation of THEDES from these components was predicted and confirmed using differential scanning calorimetry (DSC). The results indicate that the experimental effort for the identification of suitable API/excipient combinations can be drastically reduced by thermodynamic modeling leading to more efficient and tailor-made formulations in the future.
This article was published in the following journal.
Name: Molecular pharmaceutics
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Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include SOLVENTS, diluting agents, and suspending agents, and emulsifying agents. Also, ANTIOXIDANTS; PRESERVATIVES, PHARMACEUTICAL; COLORING AGENTS; FLAVORING AGENTS; VEHICLES; EXCIPIENTS; OINTMENT BASES.
Bacterial secretion systems found in bacteria that have a MYCOLIC ACID-containing outer membrane such as MYCOBACTERIACEAE; Corynebacteriaceae; and NOCARDIACEAE. These are also known as ESX secretion systems because the first to be discovered is involved in secreting major virulence factors EsxA and EsxB. There are several subtypes of T7SSs including ESX-1, ESX-2, ESX-3, ESX-4, and ESX-5 secretion systems. The subtypes share some core components including an inner membrane channel-forming ATPase complex, a membrane-anchored mycosin, and a second channel that spans the outer mycolic acid-containing membrane.
DEEP VEIN THROMBOSIS of an upper extremity vein (e.g., AXILLARY VEIN; SUBCLAVIAN VEIN; and JUGULAR VEINS). It is associated with mechanical factors (Upper Extremity Deep Vein Thrombosis, Primary) secondary to other anatomic factors (Upper Extremity Deep Vein Thrombosis, Secondary). Symptoms may include sudden onset of pain, warmth, redness, blueness, and swelling in the arm.
Gram-negative bacterial secretion systems which translocate effectors in a single step across the inner and outer membranes. The one-step secretion is carried out by a channel that passes from the CYTOPLASM, through the inner membrane, PERIPLASMIC SPACE, and outer membrane, to the EXTRACELLULAR SPACE. The specificity of type I secretions systems are determined by the specificity of the three subcomponents forming the channel - an ATP transporter (ATP-BINDING CASSETTE TRANSPORTERS); a membrane fusion protein (MEMBRANE FUSION PROTEINS); and an outer membrane protein (BACTERIAL OUTER MEMBRANE PROTEINS.)
The study of systems, particularly electronic systems, which function after the manner of, in a manner characteristic of, or resembling living systems. Also, the science of applying biological techniques and principles to the design of electronic systems.