Semisolid dosage forms

By
D. Adukondalu M.Pharm
Asst.Prof, Dpt of pharmaceutics
TPCP, Orus,Warangal.
 Contents
• Definition
• Properties
• Classification
• Theory
• Formulation
• Novel advances
• Q.A. and Q.C
• Packaging
• References
 DEFINITION

• Semisolid dosage forms are dermatological

products of semisolid consistency and applied
to skin for therapeutic or protective action or
cosmetic function
Categories of pharmaceutical Dosage Forms
 IDEAL PROPERTIES OF SEMISOLID DOSAGE
FORMS
• 1. PHYSICAL PROPERTIES: -
• a)Smooth texture
• b)Elegant in appearance
• c)Non dehydrating
• d)Non gritty
• e)Non greasy and non staining
• f)Non hygroscopic
 IDEAL PROPERTIES OF SEMISOLID DOSAGE
FORMS
• PHYSIOLOGICAL PROPERTIES: -
• g)Non irritating
• h)Do not alter membrane / skin functioning
• i)Miscible with skin secretion
• j)Have low sensitization index
• APPLICATION PROPERTIES: -
• k)Easily applicable with efficient drug release.
• l)High aqueous wash ability.
 1.2.4 STORAGE PROPERTIES

Climatic zones Definition Storage/test Example

  conditions
 
I Temp. climate 21°C + 2°C and Northern Europe,
45% RH + 5% RH Canada
II Mediterranean & 25°C + 2 °C and Southern Europe,
subtropical climate 60% RH + 5% RH Japan, US
III Hot dry climate 30°C + 2°C and Egypt, Sudan
35% RH + 5% RH
IV Hot, humid climate 30°C + 2°C and Central Africa,
75% RH + 5% RH South Pacific

Definition and storage/test conditions for four climatic zones

 TYPES OF CONVENTIONAL SEMISOLID
DOSAGE FORMS AND THEIR PROPERTIES
OINTMENTS :-
• They are soft hydrocarbon based semisolid
preparation, composed of fluid hydrocarbon meshed
in a matrix of higher melting solid hydrocarbon
petrolatum being a tasteless, odorless, unctuous
material with a melting range. Since they are greasy
nature so they stain cloths. Principle ingredients
forming the system hydrocarbon and silicon oil are
generally poor solvent for most drugs, seemingly
setting a low limit on the drug delivery capabilities
of the system.
 CREAMS
• They are viscous semisolid emulsion system with
opaque appearance as contrasted with translucent
ointments. Consistency and rheological character
depends on weather the cream is w/o or o/w.
• Properly designed O/W creams are elegant drug
delivery system, pleasing in both appearance and
feel post application.
• O/W creams are non greasy and are rinsable.
• They are good for most topical purpose and are
considered particularly suited for application to
oozing wounds
 Pastes
• Pastes are less greasy because of the absorption
of the fluid hydrocarbon fraction to the
particulates.
• ·There are two types of paste,
• a) Fatty pastes (eg: - zon paste) and
• b) Non greasy pastes (eg: - bassorin paste is also
named as tragacanth jellies since hydrophilic
component of tragacanth gels in water).
 GELS (JELLIES)
• Gels are semisolid system in which a liquid phase is
constrained within a 3-D polymeric matrix (consisting of
natural or synthetic gum) having a high degree of physical
or chemical cross-linking.
• Gels are aqueous colloidal suspensions of the hydrated
forms of insoluble medicament.
• Gels are richer in liquid than magma
• Jellies are transparent or translucent non-greasy semisolid
gels.
• Some are as transparent as water itself, an aesthetically
pleasing state, other are turbid, as the polymer is present
in colloidal aggregates that disperse light.
 POULTICES
• It is soft, viscous, pasty preparation for
external use. They are applied to skin while
they are hot. Poultice must retain heat for a
considerable time because they are intended
to supply warmth to inflamed parts of body
 6 PLASTERS

• Plasters are solid or semisolid masses adhere to

the skin when spread upon cotton felt line or
muslin as a backing material and they are mainly
used to,
• ·Afford protection and mechanical support.
• ·Furnish an occlusive and macerating action.
• ·Bring medication into close contact with the
surface of the skin
 7 RIGID FOAMS

• Foams are system in which air or some other

gas is emulsified in liquid phase to the point of
stiffening.
• E.g. shaving creams, whipped creams,
aerosolized shaving creams.
THEORY OF SEMISOLID DOSAGE FORMS

• HYDROPHILIC PROPERTIES
• RHEOLOGICAL PROPERTIES
Different rheological properties of petrolatum
base of different concentration
Plastic viscosity and thixotropic behaviour of
petrolatum and plastibase as function of
temperature
Thixotropic behaviour of petrolatum and
plastibase as a function of temperature
ROUTE OF ABSORPTION

FACTORS AFFECTING SKIN PENETRATION

 FORMULATION OF SEMISOLID DOSAGE
FORMS

Medicaments prescribed for semisolids

Disease treated API

Keratolytic Salicylic acid
Acne Sulphur, Resorcinol
Antipruritic Benzocaine, Menthol, Camphor
Emollient Lanolin
Anti-inflammatory Corticosteroid
Antifungal Benzoic acid, Salicylic acid
 BASES
• Appropriate Selection of Ointment Base: Selection of
ointment base depends on following.
• 1. Desired release rate of the drug substance from the
ointment base.
• 2. Rate and extent of topical or percutaneous drug absorption.
• 3. Desirability of occlusion of moisture from skin.
• 4. Stability of the drug in the ointment base.
• 5. Effect of drug on the consistency of base.
• 6. Easy removal of base on washing.
• 7. Characteristic of the surface to which it is applied.
 OINTMENT BASES
• Ointment bases may be classified in several ways
but the following classification based on
composition is generally used which are as follow,
• A) Oleaginous bases.
• B) Absorption bases. (Emulsifiable)
• C) Emulsion bases.
• D) Water soluble bases.
• E) Water removable bases.
 Types of creams
• 1) Sterol Creams: They are water in oil emulsions
where emulgent is wool fat or wool alcohol. Classical
example is lanolin.
• 2) Soap Creams: Triethanolamine Creams are neutral
soaps, produces o/w emulsion with oleic acid and
triethanolamine (good emulgents for liquid paraffin)
• 3) Anionic Emulsifying Wax Creams: These
emulsifiers produce oil in water type.
• 4) Cationic Emulsifying Wax Creams: These
emulsifiers produce water in oil type.
 Types of creams
• 5) Creams Emulsified with Non-ionic Surfactants:
Cream bases prepared with Self emulsifying
monostearin, a sorbitan ester, a macrogol ester, a non
emulsifying wax containing a macrogol ether etc.
• 6) Divalent Creams: Classical example is Lime creams
which is of water in oil type. Emulgent in these is Oleic
acid and Calcium hydroxide.
• 7) Vanishing Creams: They are oil in water type creams
which when rubbed onto the skin and disappear with
little or no trace of their former presence.
 FORMULATION OF SEMISOLID DOSAGE
FORMS
• ANTIMICROBIAL PRESERVATIVES
• ANTIOXIDANTS
• CHELATING AGENTS
• HUMECTANTS
• FRAGRANCES
 IDEAL EMULSIFIER

• Ideal properties of emulsifier includes,

• a) Must reduce surface tension for proper
emulsification.
• b) Prevents coalescence should quickly absorb
around the dispersed phase.
• c) Ability to increase the viscosity at low
concentration.
• d)Effective at low concentration
 Emulsifiers
Anionic Cationic Nonionic
Alkyl sulfates Quaternary ammonium Polyoxyethylene alkyl-aryl
compounds ethers
Soaps
Alkoxyalkylamines Polyoxyethylene fatty acid
Dodecyl benzene sulfonate
ester
 
Lactylates
Polyoxyethylene sorbitan
Sulfosuccinates esters
Monoglyceride sulfonates Sorbitan fatty acid esters
Phosphate ester Glyceryl fatty acid esters
Silicones Sucrose fatty acid esters
Taurates Polyoxyethylene-
polyoxypropylene block
polymers
 HLB System
HLB range Application
4–6 W/O emulsifier
7-9 Wetting agent
8 – 18 O/W emulsifier
13 – 15 Detergent
10 – 18 Solubilizers
 Gelling agents
Material % Brookfield viscosity
‘CP0’
Carbomer 941resin NF 0.15 2900
Carbomer 941resin NF 0.25 6300
Carbomer 941resin NF 0.50 44000
Carbomer 941resin NF 1.00 81000
Sodium carboxymethyl 1.50 5000
cellulose 1.50 8040
Guar gum
2.00 5200
Methyl cellulose
2.50 22800
Locust bean gum 2.50 10400
Sodium alginate
Penetration Enhancer used with
Drugs for topical semisolids
Sr. no Permeation Drugs used
enhancer
1. Menthol, carvacrol, Propranolol
linalool hydrochloride
2. Limonene Indomethacin,
ketoprofen
3. Geraniol, nerolidol Diclofenac sodium
4. Oleic acid Piroxicam
5. Lecithin Hydrocortisone
acetate, heparin
6. Propylene-glycol- Heparin
dipelargonate
7. Cyclodextrins Hydrocortisone
 Penetration enhancer
• Penetration enhancer works by,
• a) Reversibly disordering the lamellar packing
of stratum corneum.
• b) Increasing the thermodynamic activity of
the drug,
• c) Increasing the amount of drug in solubilized
form at the skin surface
Combination of Penetration Enhancer and
Cosolvent for topical semisolids
Sr. no Permeation Cosolvent Drugs used
enhancer
1. Isopropyl Propylene Diclofenac
myristate glycol sodium
2. Cineole Ethanol TRH analogue
p-Glu-3-methyl-
His-Pro amide
3. Ethanol Propylene Aspirin
glycol
 METHODS OF PREPARATION
• BY TRITURATION
• BY FUSION
• BY CHEMICAL REACTIONS
• BY OINTMENT MILLS
 NOVEL ADVANCES IN SEMISOLID
APPLICATIONS
• The advantages of nasal delivery includes

• (1)Lower doses,
• (2) Rapid local therapeutic effect,
• (3) Rapid systemic therapeutic blood levels,
• (4) rapid onset of pharmacological activity,
• (5) Few side effects.
 The attributes of a vehicle for nasal semisolids include

• (1) pH generally in the range of 5.5-7.5).

• (2) Mild buffer capacity,
• (3) Isotonic
• (4) Not modify the normal mucus viscosity,
• (5) Compatible with normal ciliary motion and ionic
constituents of nasal secretions,
• (6) Compatible with active ingredient,
• (7) Stable
• (8) Sterile
• (9) And preserved.
 Skin
• Advantage, application and uses:
• This route of drug delivery has gained
popularity because,
• (1) Provides a largest surface area
• (2) It avoids first-pass effects, gastrointestinal
irritation,
• (3) And metabolic degradation associated with
oral administration.
 OPHTHALMIC
• In ocular drug delivery, many physiological
constraints prevent a successful drug delivery
to the eye due to its protective mechanisms.
Drug loss occur via,
• (1)Less capacity of cualdy sac (up to 7.5µlit)
• (2)Dilution of drug due to lachrymal secretion.
• (3)Nasolachrymal drainage
 Rectal semisolids
• Advantage, application and uses: several advantages of using
rectal semisolids are
• (1)Large surface area
• (2)The ability to bypass first-pass liver metabolism,
• (3)Prolongs the residence time
• (4)And permeability to large molecular weight drugs, such as
peptides and proteins. (insulin gels administered deep rectally )
• less frequent risk with rectal administration of drug include skin
rash, dizziness, pain, headache, abdominal pain, nervousness,
diarrhea, feeling unsteady or clumsy, and wheezing
 Example of rectal semisolids
Sr. no Name Company Active Dosage form Use
ingredient
1. Anusol GlaxoSmithKl Starch Ointment hemorrhoids
ine
 
2. Tronolane Ross Pramoxine Cream hemorrhoids
hydrochloride
Analgesic and
Antipruritic

Applicators for rectal administration

 VAGINAL
• Advantages, applications and uses:
• The major advantages of this route include
• (1) Accessibility and large surface area,
• (2) Good blood supply,
• (3) The ability to bypass first-pass liver metabolism,
• (4) Prolongs the residence time
• (5) And permeability to large molecular weight
drugs, such as peptides and proteins.
 Examples of vaginal semisolids
Sr. no Name Company Active Dosage Use
ingredient form
1. Terazol-7 OrthoMcNeil Terconazole Cream Antifungal(a
gainst
Candida
albicans)
2. Premarin Wyeth-agerst Conjugate Cream vaginitis
estrogen
 PATENTED TECHNOLOGIES IN
SEMISOLIDS
• 1 .DELIVERY OF MONOCLONAL ANTIBODY
USING SEMISOLID DOSAGE FORM
• 2.TOPICAL DELIVERY OF VITAMIN A
• 3. DELIVERY OF EPIDERMAL GROWTH
FACTOR BY TOPICAL ROUTE
• 4 TOPICAL MEDICATIONS FOR OROFACIAL
NEUROPATHIC PAIN
• FOAM DRUG DELIVERY
 Q.A. and Q.C

• “PERFECT PRODUCT” requires an organized

effort by the entire company to prevent or
eliminate errors at every stage in production.
Raw material quality assurance monograph

Sr. no Test
A. Raw material name
 
1. Structural formula, molecular weight
2. Chemical name
3. Item number
4. Date of issue
5. Date of superseded, if any, or new material
6. Signature of writer
7 Signature of approval
 Raw material quality assurance
monograph
B. Samples
 
1. Safety requirement
2. Sample plan and procedure
3. Sample size and sample container to be use
4. Preservation sample requirement
 
C. Retest program
 
1. Retesting schedule
2. Reanalysis to be perform to assure identity, strength, quality and
purity
 Raw material quality assurance
monograph
D. Specifications wherever applicable
 
1. Description
2. Solubility
3. Identity
a. Specific chemical test
b. Infrared absorption
c. Ultraviolet absorption
d. Melting range
e. Congealing point
f. Boiling point or range
g. Thin layer, paper, liquid or gas chromatoghraphy
 Raw material quality assurance monograph
4. Purity and quality
a. General completeness of solutions, pH,
specific rotation, non-volatile residue, ash,
acid- insoluble ash, residue on ignition, loss
on drying, water content, heavy metals,
arsenic, lead, mercury, selenium, sulphate,
chloride, carbonates, acid value , iodine
value, saponification value
b. Specific quality tests ,particle size,
crystallinity characteristics ,and
polymorphic forms
c. Specific purity tests , related degenerated
products
5. Assay , calculated either on anhydrous or
hydrous basis
6. Microbial limit test, especially for raw
materials from natural sources
 
 Raw material quality assurance
monograph
E. Test procedure
 
1. Compendial USP or NF references
2. Noncompendial, detailed analytical
procedures, weights, dilutions,
extraction, normality, reagent,
instrumentation used and procedure, if
any calculation
 
F. Approved suppliers (list of prime
suppliers and other approved
alternative suppliers, if any)
 IN PROCESS CONTROL
• 1. Complete solubilization (if applicable)
• 2. pH
• 3. Viscosity measurement
• 4. Uniformity of distribution of active
ingredients
• 5. Physical stability
• 6.Measurement of density or specific gravity.
FINISHED PRODUCT SPECIFICATIONS
Pathway for finished product specification
MICROBIAL TEST
 Texture analysis
• a)Ointment flow characteristic
• b)Ointment consistency
• c)Gel strength
• d) Flavor release
• e)Sachet or Tube extrusion force
measurement
 3 CHEMICAL TESTS

• Chemical tests to be performed include,

• a.Chemical potency test
• b.Content uniformity test
• c.pH measurement
 INSTRUMENTAL ANALYSIS
• IN-VITRO RELEASE PROFILE TEST (2,
INSTRUMENTAL ANALYSIS

• ANALYSIS OF PHARMACEUTICAL CREAMS USING

UV SPECTROPHOTOMETRY
• MODIFIED USP TYPE II DISSOLUTION APPARATUS
• ANALYSIS OF GEL USING FT-NIR TRANSMISSION
SPECTROSCOPY
• ANALYSIS OF MULTIPLEXED 2DE GELS
 Packaging

• Container closures and other component part of

drug packages, to be suitable for that intended use
must not be reactive, additive or absorptive to the
extent that identity, strength, quality or purity of
drug will be affected”
• Ointment, creams and gels are most frequently
packed in 5, 15 and 30 gm tubes. Ophthalmic
ointments typically are packed in small aluminum or
collapsible plastic tubes holding 3.5 gm of ointment
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