It is widely recognized that young children cannot swallow traditional tablets, but difficulty in swallowing tablets (dysphagia) is not limited to children. In three client case studies, Senopsys’ formulation and sensory scientists collaborate with pharma companies to optimize dosage forms for ease-of-swallowing, palatability and human factors.
The client was developing a pediatric dosage form of a poorly soluble API. A number of effective solubility enhancing excipients had been identified but the client was concerned about their potential effects on palatability of the oral liquid. The sensory effects of the candidate excipients were measured over their functional usage levels to prioritize those with the lowest flavor impact for advancement.
The free base form of the API in a marketed product is known to be extremely bitter. A number of API salts were produced and evaluated using an electronic tongue (e-tongue) for confirmatory evaluation by an adult human taste panel.
Commercial eszopiclone film-coated tablets produce an unpleasant bitter taste. Senopsys developed and applied methods to measure the effects of film coatings and process variables on bitterness perceived during tablet administration.
A client was developing a pediatric dosage form of a poorly soluble API. To improve bioavailability, a hot melt extrudate was developed that had a strong intensity, lingering bitterness. The extrudate was compressed into mini-tablets and the taste masking effectiveness of tablet film coatings was explored.
Orally disintegrating tablets (ODTs) are a popular dosage form for patients who have difficulty swallowing (dysphagia). However ODT disintegration times may not meet FDA guidance (<30 seconds). Senopsys has developed protocols to reproducibly measure in-vivo disintegration time that have been used to benchmark prototypes against commercial products.
The validity of clinical trials may be questioned if subjects perceive differences between the active and placebo formulations. Senopsys regularly measures differences in the sensory attributes (taste, aroma, mouthfeel and texture) of drug products and placebos to improve palatability of drug products and develop matching placebos.
A client’s drug achieved strong positive clinical results in adults and a pediatric dosage form was urgently required. Senopsys’ initial taste assessment indicated that the API represented a difficult, multidimensional taste challenge, specifically strong intensity bitterness, tongue/throat burn and tannin mouthfeels that lingered for over 30 minutes. A mimetic system was developed to facilitate taste optimization.
A client was reformulating a drug product to improve palatability as part of a lifecycle management program. The API was characterized by a strong intensity, repugnant odor. Senopsys applied a sensory-directed headspace evaluation technique to develop a custom blend of aroma chemicals that effectively masked the offensive odor.
The client was developing an orally disintegrating tablet (ODT) form of an approved drug known to be extremely bitter. Senopsys conducted dose-response sensory analysis to establish the maximum free API concentration that could be effectively delivered in a palatable ODT and to evaluate the taste masking effectiveness of adsorption technology.
Oral spray dosing technology is capable of delivering a broad range of APIs to the systemic circulation through the highly perfused lining of the oral cavity. Senopsys followed a sensory-directed process to develop a palatable oral spray containing an extremely bitter drug in combination with a solvent system that produced trigeminal irritation.
The client needed to develop an oral dosage form to deliver an insoluble API with high loading (5gm per unit dose) at TID dosing. For chronic conditions, palatability – taste, aroma, mouthfeel and texture – takes on a particular importance. Senopsys applied its FlavorOptSM formulation development process to develop a series of palatable proof-of-concept formulations of traditional and novel dosage forms.
A large dose volume, liquid drug product was rejected by a significant number of adult clinical trial subjects due to its poor palatability. Senopsys’ initial taste assessment found the drug product to be highly salty. Senopsys reduced the perceived saltines through judicious balancing of the complementary basic tastes.