Development of suspension dosage formulation

1. Development of
pharmaceutical
formulations
Application of rheological principles in the
development of pharmaceutical
formulations
[Year]

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Dosage forms need specific flow properties so that they can be placed into a
container, remain stable over time, dispensed, handled and properly applied to the
affected area by patients. This is achieved by considering various physical and
analytical parameters.
RHEOLOGY
Rheology is the science that deals with the deformation of matters under the
influence of applied stresses.
Application of rheological principles has major importance in formulation and
analysis of pharmaceuticals as
 it will directly affect the way a drug is formulated and developed,
 the quality of the raw and finished product,
 the drug efficacy,
 the way a patient adheres to the prescribed drug,
 the physical stability and bioavailability of formulations,
 Overall healthcare cost.
Viscosity
Viscosity is a measure of a fluid’s resistance to flow i.e, the measure of a
substance’s resistance to motion under an applied force.
The following Stokes equation is familiar to most; expressing the rate of
sedimentation of suspended particles over time in a liquid vehicle:
Stokes Equation:
𝒅𝒚
𝒅𝒙
= d2
(pi – pe) g / 18ƞ
This equation estimates the sedimentation rate based on certain physical
characteristics of the suspension. These characteristics include the diameter of
suspended particles (d), acceleration due to gravity (g), density of the particles (ρi )
and external phase (ρe ), and the external vehicle viscosity (η).

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Viscosity, is a characteristic non-Newtonian viscous, is an important material
property that contributes to a fluid’s performance. Thus, fluid pharmaceutical
products do not follow Newtonian flow.
Temperature dependence
Viscosity of a liquid decreases as the temperature increases and fluidity increases
with increase in temperature.
The dependence of viscosity on temperature is expressed by an analogous to an
Arhennius equation of chemical kinetics:
ƞ = AeEvRT
k = Rate constant
A = pre-exponential factor
Ev=activation energy
R=universal gas constant
T =absolute temperature (in Kelvin)
The Ev for the flow has been found to be one third of the energy of vaporization
and it needed a free space for flow. This is because a molecule can turn back and
maneuver in a small spacethan its actual size. More energy is required to break

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bonds and permit flow in liquids composed ofmolecules that are associated
through hydrogen bonds. Thesebonds are broken at high temperature by thermal
movement, and Ev is decreased markedly.
Sedimentation:
Sedimentation means settling of particle (or) floccules occurunder gravitational
force in liquid dosage form.
Sedimentation Parameters:
Sedimentation volume (F) or height (H) for flocculatedsuspensions:
Sedimentation volume is a ratio of the ultimate volume of sediment (Vu) to the
original volume of sediment (VO) before settling.
F = V u / VO
Where, Vu = final or ultimate volume of sediment
Vo = original volume of suspension before settling
Degree of flocculation ( β )
It is the ratio of the sedimentation volume of the flocculated suspension F, to the
sedimentation volume of the deflocculated suspension, F ∞
β = (Vu/Vo) flocculated÷ (Vu/Vo) deflocculated.
The minimum value of ß is 1,when flocculated suspension sedimentation volume is
equal to the sedimentation volume of deflocculated suspension.
SUSPENSIONS
Suspensions are coarse dispersions that are biphasic liquid dosageforms of
medicaments in which the finely divided particles are dispersed in a vehicle.
The advantages of suspensions include,

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 Effective dispensing of hydrophobic drugs
 Avoidance of the use of co-solvents
 Masking of unpleasant taste of drugs
 Easy swallowing for young and elderly patients.
Ideal features of suspensiondosage form
1. The final productshould be physically, chemically, and microbiologically stable.
2. Pharmaceutical suspensionshould be aesthetically pleasing and should also have a
pleasing odour, and taste.
3. The productmust remain sufficiently homogenous for at least the period between
shaking the container and removing the required amount.
4. Suspensions must not be too viscous to pour freely from a bottle or to flow through
a needle syringe (for injectable suspensions).
5. The drug substancemust not recrystallize and/or change its polymorphic form
during storage.
6. Suspended particles should settle slowly and the sediment or creaming produced
on storage, if any, should readily redisperse upon gentle shaking of the container.
7. Parenteral and ophthalmic suspensions should be sterilizable and syringable (for
parenteral suspensions).
Stability of suspensions:
Flow behavior of a suspension system is not only dependent on the dispersed phase
(particle size, shape, morphology, concentration), but also crucially dependent on
the rheology modifiers which are used in pharmaceutical suspensions to enhance
their stability.
Rheologic modifiers
Rheologic modifiers are organic and inorganic coating adds that controlthe
rheological characteristics of liquid formulations. In coating technology, rheology
modifiers are mainly used to provide either pseudoplastic and thixotropic
properties. It includes binders (polymers, oligomers, reactive dilutants), solvents
(organic, aqueous), pigments (organic, inorganic) and fillers and additives
(stabilizers, inhibitors, catalysts).

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Buffer and pH modifying agents:These agents are added to stabilize the
suspensions by controlling the altering pH conditions. Citrate buffer are used to
stabilize suspensions in the range pH 3-5 phosphatebuffers are used to stabilize
suspensions in the range of pH 7-8.
Thickeners/Viscositymodifiers: these agents are used to increase the viscosity of
a suspension without substantially changing its other properties and decreases
sedimentation. They can be hydrophilic colloids or polymers.
Polymers of high molecular weight and composed ofwater-loving functional
groups can greatly help to controlviscosity, rheology and thus, stabilizing the
formulation. However, the interaction of these polymers with an aqueous medium
will crucially depend on the nature of the aqueous medium. E.g., gum acacia, corn
starch.
Flocculating agents:Addition of flocculating agents help to stabilize the
suspension by decreasing inter-particle attraction which helps to prevent
aggregation and caking overtime. Eg, Aluminium chloride is used as a flocculating
agents at concentrations of 0.01%-1%.
Coloring agents:They are added to impart distinctive color to suspension and
improve elegance. Eg, D&C Yellow#10 in Ibuprofen suspension.
Wetting agents:Surfactants or Wetting agents are used in suspension to reduce
the interfacial tension between solid particles and vehicle thereby promoting
wetting and deflocculation of particles. E.g., glycerin.
Preservatives:They are added to prevent microbial growth in formulated
suspensions. Eg, Propylene glycol.

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Ciproxin 250 mg/5 mL granules and solvent for oral suspension
Activeingredient – ciprofloxacin
Used as - Antibiotic, Antiprotozoal medication.
Inactiveingredients:
Sweetening agent - Sucrose/Neotame-3to10% concentration
Flavoring agent - mixed fruit powder (orange, banana, pineapple, strawberry)-0.2
to 1% concentration
Buffering agents – sodium citrate, potassium phosphate, citric acid – 0.2 to 1%
concentration
Suspending agent- Xanthan gum, sodium CMC, hydroxypropyl cellulose-0.1-
0.5% concentration
Suitable solvent- Isopropyl alcohol, methylene chloride, water
Lubricants - magnesium sterate, sodium steryl fumarate 0.05-0.2%

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Other excipients - cellulose, starch, lactose 0-15%
Vehicle - purified water
Co-solvent- glycerin
REFERENCE:
 http://www.sips.org.in/wp-content/uploads/2020/03/SUSPENSION-
_BP103TP.pdf
 file:///C:/Users/VM-MED/Downloads/rheology-in-pharmaceutical-
formulationsa-perspective-2329-6631.1000108%20(2).pdf
 Mastropietro DJ, Nimroozi R, Omidian H (2013) Rheology in
Pharmaceutical Formulations-A Perspective. J Develop Drugs 2: 108.
doi:10.4172/2329-6631.1000108
 Martin’s Physical Pharmacy and Pharmaceutical sciences by Patrick J. Sinko
 Physical pharmaceutics by Manavalan and Ramasamy.
 file:///C:/Users/VM-MED/Downloads/rheology-in-pharmaceutical-
formulationsa-perspective-2329-6631.1000108%20(2).pdf