S ENS OR
Y-DIRECTED
FORMULATIONS
Taste Optimization of a Model Oral Spray Drug Product
By: Jeffrey H. Worthington, MBA; David A. Tisi, MS; Frank E. Blondino, PhD; and Foyeke O. Opawale, PhD
INTRODUCTION
Technology advances are leading to the development of novel oral dosage forms that may provide faster onset
of action, fewer side effects, and improved patient dosing (convenience). One such technology is oral sprays.
NovaDel Pharma Inc. utilizes oral spray systems to deliver a broad range of APIs to the systemic circulation through
the highly perfused lining of the oral cavity. NovaDel’s core technology offers substantial benefits compared to other
modalities of drug administration, including faster onset of action, increased drug bioavailability due to avoidance
of first-pass effect in the liver, avoiding the need to take medication with water, and avoiding the need to swallow.
Drug delivery via the oral cavity may also minimize inter- and intra-subject pharmacokinetic variability related to
stomach-emptying time, food effects, and enzymatic or chemical degradation in the gastrointestinal tract. The main
characteristic of the technology is the delivery of solution formulations of API to the oral cavity in the form of a
spray. However, many APIs are bitter or have other undesirable taste characteristics that need to be masked in order
to develop palatable, patient-acceptable drug products. The following discussion will review the approach for
developing a palatable oral spray for a model API.
DEVELOPING PALATABLE
DRUG PRODUCTS –
A STAGED APPROACH
The development of palatable drug
products can be a daunting challenge.
This is exacerbated by the general
misconception in the pharmaceutical
industry that taste perception cannot be
quantified. Nothing could be further
from the truth - sensory science is a core
competency of most consumer packaged
goods companies that compete on the
basis of product aesthetics.
Pharmaceutical companies, of course,
have the added complexity of managing
human exposure to drug substances,
which is their core competency.
It is nearly impossible to develop a
palatable drug product without knowing the
taste characteristics of the API. Accordingly,
Senopsys LLC followed the two-stage Taste
Assessment and Taste Optimization
development approach described herein.
unflavored, unsweetened oral spray
excipient system composed principally
of solubilizers. Five doses were
dispensed in a fixed-dose volume of
two 100 microliter actuations to deliver
1, 2, 4, 6, and 8 mg. This dose volume
was set to maximize residence time in
the oral cavity and minimize the
swallowing reflex. At this volume, the
upper end of the dose-response was
bound by the solubility of the API.
patient acceptability; therefore, it is
critical that each be evaluated.
Following two spray actuations directed
to the tongue, the initial flavor
characteristics were measured during
the first 10 to 20 seconds. The
aftertaste characteristics were measured
at eight time intervals (1, 3, 5, 10, 15,
20, 25, and 30 minutes).
The drug product was under an
Investigational New Drug application
and accordingly, the study was
conducted under the auspices of an
external Institutional Review Board.
The objective of this assessment
was to develop the dose-response
function for the model API in an
Taste Profiling Procedure
The oral sprays were evaluated by
trained and experienced pharmaceutical
sensory panelists using the Flavor
Profile method of descriptive sensory
analysis.1 Flavor Profile entails the
identification and measurement of the
sensory attributes of products, eg,
texture, aroma, taste, and mouthfeel.
Reference standards are used to define
the attributes, and reference scales for
intensity of different attributes ensure
consistent application of the
measurements across panelists and
reproducibility across evaluations.
Both the initial flavor and
aftertaste characteristics of drug
products are important determinants of
Dose/Response Results
The challenge for many drug
products is to mask the undesirable
sensory characteristics of the API and
excipients in the initial flavor and
throughout the aftertaste (eg, bitterness,
burn, stinging, and drying). Visualizing
the data as a function of time provides
valuable diagnostic information (Figure
1). A series of time-intensity plots were
prepared for the critical sensory
attributes. In each time-intensity plot,
the area above a slight intensity on the
Flavor Profile scale (>1) has been
shaded. Based on experience across a
