semisolids

Semisolid dosage forms

ByD. Adukondalu M.Pharm

Asst.Prof, Dpt of pharmaceuticsTPCP, 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.

Definition and storage/test conditions for four climatic zones

Climatic zones Definition

Storage/test conditions

Example

I Temp. climate 21°C + 2°C and 45% RH + 5% RH

Northern Europe, Canada

II Mediterranean & subtropical climate

25°C + 2 °C and

60% RH + 5% RH

Southern Europe, Japan, US

III Hot dry climate 30°C + 2°C and 35% RH + 5% RH

Egypt, Sudan

IV Hot, humid climate 30°C + 2°C and 75% RH + 5% RH

Central Africa, South Pacific

1.2.4 STORAGE PROPERTIES

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

Disease treated API Keratolytic Salicylic acid

Acne Sulphur, Resorcinol Antipruritic Benzocaine, Menthol, Camphor Emollient Lanolin

Anti-inflammatory Corticosteroid Antifungal Benzoic acid, Salicylic acid

Medicaments prescribed for semisolids

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

EmulsifiersAnionic Cationic Nonionic

Alkyl sulfates

Soaps

Dodecyl benzene sulfonate

Lactylates

Sulfosuccinates

Monoglyceride sulfonates

Phosphate ester

Silicones

Taurates

Quaternary ammonium compounds

Alkoxyalkylamines

Polyoxyethylene alkyl-aryl ethers

Polyoxyethylene fatty acid ester

Polyoxyethylene sorbitan esters

Sorbitan fatty acid esters

Glyceryl fatty acid esters

Sucrose fatty acid esters

Polyoxyethylene-polyoxypropylene block

polymers

HLB SystemHLB range Application

4 – 6

7 - 9

8 – 18

13 – 15

10 – 18

W/O emulsifier

Wetting agent

O/W emulsifier

Detergent

Solubilizers

Gelling agentsMaterial % Brookfield viscosity

‘CP0’ Carbomer 941resin NF

Carbomer 941resin NF

Carbomer 941resin NF

Carbomer 941resin NF

Sodium carboxymethyl cellulose

Guar gum

Methyl cellulose

Locust bean gum

Sodium alginate

0.15

0.25

0.50

1.00

1.50

1.50

2.00

2.50

2.50

2900

6300

44000

81000

5000

8040

5200

22800

10400

Penetration Enhancer used with Drugs for topical semisolids

Sr. no Permeation enhancer

Drugs used

1. Menthol, carvacrol, linalool

Propranolol hydrochloride

2. Limonene Indomethacin, ketoprofen

3. Geraniol, nerolidol Diclofenac sodium 4. Oleic acid Piroxicam 5. Lecithin Hydrocortisone

acetate, heparin 6. Propylene-glycol-

dipelargonate Heparin

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 enhancer

Cosolvent Drugs used

1. Isopropyl myristate

Propylene glycol

Diclofenac sodium

2. Cineole Ethanol TRH analogue p-Glu-3-methyl-His-Pro amide

3. Ethanol Propylene glycol

Aspirin

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 semisolidsSr. no Name Company Active

ingredient Dosage form Use

1. Anusol GlaxoSmithKline

Starch Ointment hemorrhoids

  2. Tronolane Ross Pramoxine

hydrochloride Cream hemorrhoids

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 semisolidsSr. no Name Company Active

ingredient Dosage form

Use

1. Terazol-7 OrthoMcNeil Terconazole Cream Antifungal(against

Candida albicans)

2. Premarin Wyeth-agerst Conjugate estrogen

Cream vaginitis

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

References

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