Semi-Solid Dosage Form

Semisolid Dosage Form

• Not that compact like solid

• Not free flowing as liquid

• But more on solid type

Unshaped: cream, ointment (most common), paste, gel

Shaped: suppository, pessary

Semisolid Based on physical shape

Unshape: COPG

Shaped: SuPe

Systemic: transdermal(drug pass thru skin)/Suppository

Local/topical

Semisolid Based on administration route

Highly viscous: paste

Less viscous: cream, gel

Semisolid Based on rheological properties

One phase system: gel, liniment, ointment, paste, suppository

Two phase system: cream, emulsion (o/w or w/o)

Semisolid Based on phase

Unguentum

Latin word for ointments

Ointments

• Solutions or dispersions of one or more medicaments in nonaqueous bases

• Intended to adhere to the skin or certain mucous membranes

• Classification: epidermic, endodermic, diadermic

• Uses: vehicle for medicaments, emollients, skin protectives

• Diffusion rate in ointment bases is pH dependent.

• Drug release depends on vehicle composition & drug concentration incorporated in it

• Hydrocarbon (Oleaginous) - occlusive; has most lipid content

• Absorption bases (anhydrous)

• Water-removable bases

• Water-soluble bases (greaseless) - no lipid content

Ointment Bases: Classification

Hydrocarbon

• primarily contains lipid

• Examples: Petrolatum, Yellow ointment, White ointment, Paraffin, Mineral oil

Yellow ointment ingredients

95% Yellow petrolatum and 5% yellow wax

White ointment ingredients

95% white petrolatum and 5% white wax

Absorption bases

• have the ability to absorb small amount of liquid and moisture

• Examples: Hydrophilic petrolatum, Anhydrous lanolin, Aquaphor, Cold cream

Water-removable bases

• hydrophilic content

• Example: Hydrophilic ointment USP

Water-soluble bases

• no lipid content

• Example: Polyethylene Glycol ointment

• Drug release rate from the ointment base.

• Percutaneous absorption enhancement.

• Drug stability & incompatibility in the ointment base.

• Drug’s influences on the consistency of the ointment base.

Selection of ointment base

✔ Nonirritating, nondehydratinhg, non greasy

✔ Compatible with common medicaments & stable

✔ Easily removed with water

✔ Good absorptive properties

✔ Good drug release properties from the ointment base

Ideal properties to consider

• incorporation

• fusion

Ointment preparations (FI)

Incorporation

• also known as levitation

• Components are mixed (mortar pestle or spatula) until a uniform preparation is attained

• Solids: Use levigating agents (ie. mineral oil, glycerin)

Fusion

• also known as melting

• Components are combined, melted together, & cooled with constant stirring until congealed.

• Cons: Heat-labile or volatile substances are added last when the mixture temperature is low enough.

• Small scale production: porcelain dish or glass beaker

• Large scale production: steam-jacketed kettle

Creams

• Viscous liquid or semisolid emulsion of either o/w or w/o type

• Classified as water-removable bases & widely used in cosmetics

• Opaque appearance that can penetrate the outer skin layer to provide emolliency

• Reduces surface roughness & increases the hydrophilic properties of skin

• Examples: shaving creams, hand creams, foundation creams, vanishing cream

• elegant, nongreasy, water-washable, suited for oozing wounds

Example of O/W type of cream (hydrophilic)

• Examples: cold creams, emollient cream

• more moisturizing that prevent excessive moisture loss

Example of W/O type of cream (lipophilic)

Galen’s Cerate

Cold creams are also known as _______

Pastes

• Topical preparations with high percentage of insoluble solid (> 25%)

• Its stiffness and impenetrability makes it undesirable to be applied on hairy skin parts

• Less greasy & forms unbroken water-impermeable film that can absorb serous secretions

Zno pasta

• Fatty paste

• Also known as lassar’s Plain Zinc Paste

• 25% + Zno + starch + white petrolatum

Bassorin paste (tragacanth jelly)

Non greasy paste

Glycerogelatins

Plastic masses that are melted before application, cooled to

slightly above body temperature and applied to the affected area

with a fine bru

• Glycerin:40% (glyceRIN – quaRINta)

• Water: 35% (waTER – TERTI FIVE)

• Gelatin: 15% (gelaTIN – fifTIN)

• Active Ingredient (i.e., ZnO for varicose veins before): 10%

Glycerogelatins is composed of

❑ Partition coefficient

❑ Moisture and temperature in the environment of the skin

❑ Pathological injury to the skin

❑ Type of vehicle used

Factors influencing drug absorption through the skin

• Petrolatum & Mineral oil

• Prefer low viscosity oils: less tacky & greasy

Hydrocarbons

Paraffin, Ceresin wax (mixture of ozokerite & parafin wax)

Hydrocarbon waxes

• Peanut oil, olive oil, almond oil, sesame oil

• For trace metal contaminants, add antioxidants

  (ex. BHT, BHA, propyl gallate) & chelating agents

  (ex. EDTA)

Oleaginous substances

• Stearic acid: cream consistency & matt effect on the

  skin; combined with KOH, triethanolamine, cetyl

  alcohol

• Na stearate: firm consistency

• Lanolin, beeswax, carnauba wax, candelilla wax,

  silicones

Fatty acids & alcohols

Emulsifiers

• Polyvalent ions (ex. Mg, Ca, Al) stabilize w/o emulsion by crosslinking the polar groups of fatty materials.

• Mg Al silicate: thickener, SA, o/w emulsion stabilizer

• Cationic or nonionic emulsifiers are preferable for drugs requiring acidic pH

• Glycerin, propylene glycol, sorbitol 70%

• Prevents dehydration & crusting

• Improves consistency & rub-out qualities

Polyols / Humectants

• Must be uniformly dispersed to assure product homogeneity & grittiness

• Solid should be impalpable to touch, otherwise grittiness results

Insoluble powders

• Considerations: drug solubility & stability, nature of skin lesion

• Bases: hydrocarbon, absorption, water-removable, water-soluble

Vehicle types

• BHA, BHT, propyl gallate

• Considerations: tonicity, irritating potency, compatibility,

  odor, discoloration, solubility, stability

Antioxidants

Preservatives

Addition of perfumes, high glycerin conc, & electrolytes make the environment less favorable to microbial growth, thus enhance preservative effectiveness.

TAT broth consisting of typtone (20%), azolectin (0.5%), & polysorbate 20 (4%)

Preservative Efficacy Test

• Cracked cream

• Hydrolysis or Oxidation

• Discoloration

• Precipitation

Incompatibility detection

• Rapid cooling of the mixture

  • Phase separation

• Incorporation / entrapment of too much air

  • Grainy texture of the product

• Uneven heat distribution in the mixing vessel

  • Uneven mixing

• Unsanitary facility & equipment

  • Product spoilage

Common manufacturing problems

suppositories

medicated solid dosage form intended for use in the rectum, vagina, and urethra

local action

local/systemic action: emollients

local action

local/systemic action: astringents

local and systemic action

local/systemic action: antibacterial agents

local action

local/systemic action: hormones, steroids, and local anesthetics

systemic action

local/systemic action: analgesics

systemic action

local/systemic action: antispasmodics

systemic action

local/systemic action: sedatives and tranquilizers

• torpedo

• bullet-like

rectal suppository

• shape - adult: t___, b___-like shape, “little finger”

pencil-like

rectal suppository

• child - adult: p___-like

• adult: 2 g

• child: 1 g

rectal suppository

• weight - adult: ___ g

• weight - child: ___ g

• adult: 32 mm

• child: 16 mm

rectal suppository

• size - adult: ___ mm

• size - child: ___ mm

pessaries

other name for vaginal suppositories

bougies

other name for urethral suppositories

5 g

vaginal suppository

• weight - adult: ___ g

• male: 4 g

• female: 2 g

urethral suppository

• weight - male: ___ g

• weight - female: ___ g

pencil-shaped

urethral suppository

• shape: p___-shaped

• globular

• oviform

• cone-shaped

vaginal suppository

• shape

  • g___

  • o___

  • c___-shaped

• 37.5 °C

• non-toxic and non-irritating 

• compatible

suppository base ideal properties

• melts at rectal temperature: ___ °C

• non-t___ and non-i___ to sensitive and inflamed tissues

• physically stable and c___ with a variety of drugs

• convenient for the patient to handle 

• does not break, melt, leak from the rectum

• stable on storage; does not change in color, odor, and drug release pattern

fatty (oleaginous)

cocoa butter - fatty (oleaginous) / water-soluble / water-dispersible

fatty (oleaginous)

fattibase - fatty (oleaginous) / water-soluble / water-dispersible

fatty (oleaginous)

wecobee bases - fatty (oleaginous) / water-soluble / water-dispersible

fatty (oleaginous)

witepsol bases - fatty (oleaginous) / water-soluble / water-dispersible

water-dispersible

polyoxyl 40 stearate - fatty (oleaginous) / water-soluble / water-dispersible

water-soluble

glycerinated gelatin - fatty (oleaginous) / water-soluble / water-dispersible

water-soluble

PEG mixtures - fatty (oleaginous) / water-soluble / water-dispersible

cocoa butter

most widely used based for rectal suppositories 

rectal

cocoa butter is most widely used based for ___ suppositories

Theobroma cacao

source of cocoa butter

cocoa butter

base that exhibits polymorphism

• 18 °C

• 22 °C

• 28 °C

• 34.5 °C

polymorphism of cocoa butter

• γ (gamma) = ___ °C

• α (alpha) = ___ °C

• β (beta) = ___ °C

• β’ (beta-prime) = ___ °C

beta-prime

polymorphism of cocoa butter used for rectal suppositories

40 to 50 °C

maximum fusion temperature for cocoa butter ___-___ °C

coconut oil

wecobee source

• saturated fatty acids

• C12 to C18

witepsol - triglycerides of s___ fatty acids (C__ to C__)

lauric acid

witepsol - composition

glycerinated gelatin

most widely used based for vaginal suppositories

polyethylene glycol

base that does not melt at body temperature but rather dissolves slowly in the body’s fluids

miscellaneous

base that are generally combinations of lipophilic and hydrophilic substances (i.e., polyoxyl 40 stearate)

miscellaneous

polyoxyl 40 stearate is a type of ___ base

• oxidation

• crystallization 

• > 50%

• preservatives 

special formulation problems: water

• accelerates fast o___ 

• c___ of dissolved substances 

• absorption of water-containing suppositories is enhanced if an o/w emulsion exists with > ___% of the water in the external phase

• to solve this: addition of ___ is needed

• glycerinated gelatin

• dry climates

special formulation problems: hygroscopicity 

• g___ g___ suppositories lose moisture by evaporation in d___ climates and absorb moisture under conditions of high humidity

• to solve this: add in containers that cannot absorb moisture

• polyethylene glycol

• stability testing

special formulation problems: incompatibilities

• p___ g___ bases crystalllize with Na barbital, salicylic acid, and camphor

• remedy: s___ testing

1. hand molding

2. compression

3. pour molding

4. automatic molding machine

4 manufacturing methods

1. h___ molding

2. c___

3. p___ molding

4. a___ molding machine

dissolution test

rotating dialysis cell method is used for what QC test

breaking test

rheometer is used for what QC test

liquefaction (softening time)

u-tube apparatus is used for what QC test

• cocoa

• acidic

• refrigerator

packaging considerations & problems encountered

• individually overwrapped with tin or aluminum foils

  • c___ suppositories form a white powdery surface deposit

  • pinholes by a___ suppositories

• compartment cardboard boxes or plastic containers

• protected from heat, moisture, and dry air by storing inside the r___

• electroporation

• sonophoresis

physical penetration enhancers

• electrically based: e___, iontophoresis, s___, photomechanical waves

release part or protective peel strip

TDDS part: removed before application to allow drug release

adhesive layer

TDDS part: maintain contact with the skin

drug reservoir

TDDS part: stores and releases drug

backing layer

TDDS part: protects drug

peel adhesion test

measure the force required to peel away a transdermal patch attached to a stainless steel test panel substrate

tack test

measure the tack adhesive properties

shear strength test or creep compliance test

measure the cohesive strength either through dynamic or static test

paddle over disk method

usp apparatus 5 name

rotating cylinder method

usp apparatus 6 name