Emulsion dosage forms are designed to meet the following quality attributes:
Quality attributes
Emulsion
dosage forms are designed to meet the following quality attributes:
1.
Uniformity of
content (dose-to-dose
within the same bottle and bottle-to-bottle):
All the doses dispensed from a given multidose con-tainer should have
acceptable uniformity of drug content. In addition, the drug content must be
uniform between different bottles of a given batch of emulsion.
2.
Separation volume or
creaming:
Once an emulsion has been left undis-turbed for some time, it may show some
degree of separation of the dis-persed phase from the dispersion medium. For
example, in the case of an o/w emulsion, creaming
of an emulsion is sometimes observed, which indicates a higher concentration of
the dispersed oil phase in the top layer of the emulsion. This top phase is
visually distinguishable from the bot-tom layer due to greater light
obscuration and diffraction by a higher con-centration of the dispersed phase
globules. More the concentration of the dispersed phase, more the light
obscuration in a smaller thickness of the creamed
layer and greater the instability. Thus, the proportion of the volume occupied
by the separated phase is an indicator of physical insta-bility of the
emulsion. Higher this volume, more stable is the emulsion.
3.
Dispersed phase size
distribution:
Size distribution of dispersed phase should
remain fairly constant during the shelf life of the emulsion. Brownian motion,
agitation during handling, and gravitational motion of the dispersed phase lead
to collisions of globules with each other, which can cause coalescence or
agglomeration resulting in an increase in the size of the dispersed phase. A
change in the dispersed phase globule size on storage is indicative of
inherently low physical stability of the emulsion.
4.
Drug concentration: In cases where
drug concentration in the emul-sion is close to the drug solubility,
crystallization can sometimes occur due to temperature fluctuations during
storage, preferential evapora-tive loss of one phase, incompatibility with
packaging components, or unintended nucleation. Crystal growth can be inhibited
by the use of appropriate solubilizers and surfactants, and by formulating an
emul-sion at a lower concentration than the drug’s thermodynamic solubil-ity.
Changes such as drug crystallization or evaporative loss of the continuous
phase can reflect changes in the drug concentration during storage stability or
shelf life.
5.
Palatability: Use of an emulsion
dosage form can improve the palat-ability of particularly bitter drugs by
dissolving them in the dispersed phase. However, incorporation of the drug in
the dispersed phase may not be adequate because some drug would inadvertently
parti-tion into the continuous phase depending on the partition coefficient
(logP) of the compound. Palatability of the emulsion can be increased by the
use of sweeteners, flavors, and colorants. In certain cases, specialized
taste-masking approaches, such as complexation, may be needed. These
considerations, of course, are not pertinent for paren-teral emulsions. In the
case of parenteral emulsions, tissue irritability and osmotic pressure are
important considerations.
6.
Redispersability: A separated or
creamed emulsion should readily redisperse
upon gentle shaking of the container.
7.
Absence of phase
separation:
Coalescence leading to phase separation is
irreversible. Although creaming of an emulsion is, to some extent, unavoidable,
the dispersed phase should not coalesce and separate from the dispersion
medium. This needs to be designed into the formu-lation by the use of right
surfactants in an appropriate concentration.
8.
Deliverability: The labeled number
of doses and the labeled amount of
emulsion should be deliverable from a bottle under the normal dis-pensing
conditions by a patient. This is usually ensured by pouring out the labeled
number of doses from the container and ensuring that the remaining dose can be
poured completely within a reasonable period of time.
9.
Flow: The emulsion must
not be too viscous to pour freely from a bottle
or to flow through a needle syringe or an IV infusion set (for parenteral
emulsions).
10. Lack of microbial growth: Use of antimicrobial preservatives
could be sufficient for oral and
topical emulsions, whereas parenteral, nasal, and ophthalmic suspensions must
be sterile.
11. Physical integrity: The dosage form should not show
any unexpected change in color, or
any other change in physical appearance or per-ception of the dosage form, such
as odor, that may alarm the patient and/or the health-care provider with
respect to the physical integrity of the emulsion.
12. Adhesion to the package: Preferential adsorption or
adhesion of one phase or component of
the emulsion, such as the drug, the chelating agent, or the emulsifier, can
adversely affect the uniformity and sta-bility of an emulsion.
13. Leachables and extractables: Primary packaging
components of the emulsion can leach
out small amounts of chemical components used in the manufacturing of those
components. This behavior can be exacer-bated at certain pH values of the
formulation. The packaging compo-nents must be selected appropriately, and
their compatibility with the emulsion determined to make sure no chemical
compounds leach into or are extracted by the emulsion from the container on
storage.
14. Chemical stability: There should not be any
unacceptable chemical degradation of
the drug during the shelf life of the product under rec-ommended packaging and
storage conditions. The drug product must meet the predetermined requirements
of maximum levels of known and unknown impurities.
15. Drug release: Since an emulsion contains the
drug in the dispersed phase, the
release of drug from the dispersed phase into an aqueous solution in an
appropriate dissolution vessel is quantified and con-trolled as an indicator of
its bioavailability. This could be particularly important for semisolid
emulsions.
In
addition, topical emulsions should be fluid enough to spread easily but not so
fluid that the emulsion runs off the surface too quickly. The emulsion must dry
quickly and provide an elastic film that should not be too oily. In addition,
the dosage form must have pleasant color and odor, although a sweetener is not
needed.
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