II.

Semisolid Dosage Forms

1. Ointments

2. Creams

3. Gels

4. Miscellaneous Semisolids:

Pastes

Plaster

Glycerogelatins

1. Ointments
are semisolid preparations intended for external application to the skin or mucous membranes
may be medicated or not
Uses:
Emollients  make the skin more pliable
Protective Barriers
Vehicles  in which to incorporate medication
Ointment Bases:
1. Oleaginous Bases (Hydrocarbon Bases)
characteristics:
 greasy
 non-water washable
 offer the best emollient & occlusive effects
a. Petrolatum, USP
purified mixture of semisolid hydrocarbon obtained from petrolatum
aka Yellow Petrolatum (Vaseline®), Petrolatum Jelly
b. White Petrolatum, USP (White Vaseline®)
purified mixture of semisolid hydrocarbon, obtained from petroleum that has been
nearly or wholly decolorized.
c. Yellow Wax  wax obtained from the honeycomb of Apis Mellifera (European
Honeybee)
d. Yellow Ointment (Simple Ointment) yellow wax + Petrolatum USP
e. White Ointment, USP white wax (yellow wax that has been bleached) + White
petrolatum, USP
2. Absorption Bases
emollient & occlusive effect
greasy; non-water washable
 may permit the incorporation of aqueous solutions in small amount
a. Hydrophilic Petrolatum, USP (Aquaphor®) stearyl alcohol + white wax + cholesterol +
white petrolatum
 b. Lanolin (Wool Fat) wax-like substance from the wool of the sheep (Ovis arie)
Anhydrous Lanolin (Woolfat)  NMT 0.25% moisture
Hydrous Lanolin (Woolfat)  NMT 25% moisture
Modified Lanolin  lanolin that has been processed to remove free lanolin alcohols +
excess detergents
3. Water Removable Bases (Water-washable Base)
resembles o/w emulsion & creams
may dilutes with water or aqueous solutions
have the ability to absorb serous discharges
Example: Hydrophilic Ointment, USP
4. Water Soluble Base (Greaseless Base)
do not add large amount of H2O into the base because they soften easily
complete water washable
do not contain oleaginous components
used for the incorporation of solid substances
Example: PEG Ointment, NF

Methods in the Preparation of Ointments:

a. Incorporation  mixing of all components, until a uniform mixture is achieved using
mortar & pestle, or a spatula
Incorporation of Solid  preparing an ointment by Spatulation
b. Fusion  mixing all of the component by melting w/ constant stirring then allowed to
cool until congealed.

Bleeding  liberation oil or water from ointment bases

2. Creams  are semisolid preparations containing one or more medicinal agents dissolve or
dispersed in either a w/o or o/o emulsion or in another type of water-washable base
 more preferred than ointments
 because of the ease in spreadability
 less viscid (sticky) & lighter than ointments
 are considered to have grater aesthetic appeal fo their non-greasy character, ability to vanish
into the skin upon rubbing, & ability to absorb serous discharges from skin lesions
 Example:
Vanishing Cream  o/w emulsion
 stearic acid Cold Cream (w/o emulsion)
3. Gels  are semisolid consisting of dispersions of small or large molecules in an aqueous liquid
vehicle rendered jellylike by the addition of a gelling agent
 among the gelling agent used:
synthetic macromolecules: Carbomer 934
cellulose derivatives: Carboxymethylcellulose/ Hydroxypropyl Methylcellulose
natural gums: Tragacanth  aka “Jellies”
 Two Types of Gels:
(a) Single-Phase Gels  gels in which macromolecules are distinguished somewhat uniformly in a
liquid vehicle & no apparent boundary can be seen
(b) Two-Phase Gels  gels made up of flocculated small distinct particles
 Ex:Milk of Magnesia(7-8.5%MgO)
Classifications of Gels:
 First Classification Scheme:
1. Inorganic Hydrogels  usually two-phase system
Ex: Aluminum Hydroxide Gel
Bentonite Magma (also an ointment base)
2. Organic Gels  usually single-phase system
Ex: Carbopol Tragacanth

 Second Classification Scheme:

1. Hydrogels  disepersible as colloidal or soluble in water; they include organic
hydrogels, natural & synthetic gums, & inorganic hydrogels.
2. Organogels  include the hydrocarbons, animal& vegetable fats, soap base, greases,
& the hydrophilic organogels.
Example:
Petrolatum (semisolid gel)
Plastibase (hydrocarbon type, combination of mineral oils & heavy hydrocarbon waxes)

4. Miscellaneous Semisolids
Pastes  are semisolid preparations intended fro application to the skin
 are generally contain a larger proportion of solid material than ointments (25% more
of solid particles)
 stiffer/harder than ointments, so they remain in place after application & are
effectively employed to absorb serous secretions
 easier to spread & remove than oitment
 can be prepared in the same manner as ointments
CI: Not applied on hairy part of the body
Use: to absorb serous secretions (for protective action)
Example: Zinc Oxide Paste
-Lassar’s Plain Zinc Paste
-25% each of Zinc Oxide Paste Starch w/ white petrolatum
Plasters  solid or semisolid adhesive masses spread on a backing of paper, fabric, moleskin, or
plastic.
 are applied to the skin to provide prolonged contact at the site
Use: To prolong the contract of the active ingredient to the site of absorption
Examples: Salicylic Acid Plaster (10-40%) -use to remove corns & warts
Glycrogelatins  are plastic masses containing:
Glycerin (40%)
Water (35%)
 Gelatin (15%)
Medicinal Substance (10%) are applied to the skin for the long term.
Example: Zinc Gelatin (treatment of varicose ulcers)

NOTES . . .

Epicutaneous Route

 drugs are administered topically, or applied to the skin, for their action at the site of
application or for systemic drug effects

Semisolid: Ointments, Creams, Pastes

Solid: Medicinal Powders  are intimate mixture of medicinal substances usually in an

inert base such as Talcum powder or Starch

Liquid: Lotion  are emulsions or suspensions generally in an aqueous vehicle

may be preferred over semisolid preparations because of their nongreasy character &
their increased spread ability over large areas of skin.

III. Transdermal Drug Delivery System often called as “Transdermal patches” facilitate the passage of
the drug from stratum corneum to the systemic circulation

Two Types of TDDSs:

1. Monolithic Transdermal System  incorporate a drug matrix layer between the backing & frontal
layers

2. Membrane-controlled Transdermal System  are designaed to contain a drug reservoir or pouch,

usually in liquid or gel form, a rate-controlling membrane, & backing, adhesive & protecting layer
Advantages & Disadvantages of TDDSS

Advantages:

1. They can avoid gastrointestinal drug absorption difficulties.

2. They can substitute for oral administration of medication when that route is unsuitable, as
with vomiting and diarrhea.

3. They avoid the first-pass effect.

4. They are noninvasive, avoiding the inconvenience of parenteral therapy.

5. They provide extended therapy with a single application.

6. The activity of drugs having a short half-life is extended through the reservoir of drug

7. Drug therapy may be terminated rapidly.

 8. They are easily and rapidly identified in emergencies.

Disadvantages:

1. Only relatively potent drugs are suitable candidates for transdermal delivery because of the natural
limits of drug entry imposed by the skin’s impermeability.

2. Some patients develop contact dermatitis at the site of application from one or more of the system
components, necessitating discontinuation.

General Clinical Considerations in the Use of TDDSs

1. Percutaneous absorption may vary with the site of application.

2. TDDSs should be applied to clean, dry skin that is relatively free of hair and not oily, irritated,
inflamed, broken, or callused.

3. Use of skin lotion should be avoided at the application site because lotions affect skin
hydration and can alter the partition coefficient between the drug and the skin.

4. TDDSs should not be physically altered by cutting (as in an attempt to reduce the dose) since
this destroys the integrity of the system.

5. A TDDS should be removed from its protective package, with care not to tear or cut into the
unit.

6. A TDDS should be placed at a site that will not subject it to being rubbed off by clothing or
movement (as the belt line).

7. A TDDS should be worn for the full period stated in the product’s instructions.

8. The patient or caregiver should be instructed to cleanse the hands thoroughly before and
after applying a TDDS.

9. If the patient exhibits sensitivity or intolerance to a TDDS or if undue skin irritation results, the
patient should seek reevaluation.

10. Upon removal, a used TDDS should be folded in half with the adhesive layer together so that
it cannot be reused. The used patch, which contains residual drug, should be placed in the
replacement patch’s pouch and discarded in a manner safe to children and pets

Factors Affecting Percutaneous Absorption:

1. Drug Concentration
2. Large Area of Application
3. Physicochemical attraction to the skin
4. Drugs with molecular weights of 100-800
5. Hydration of the skin
6. Percutaneous absorption
7. The longer the medicated application remain on the skin, the greater is the
total absorption.
Layers of TDDSs:

a. Occlusive Backing Layer  to protect the system form environment entry & from loss of drug from the
system or moisture from the skin

b. Drug Reservoir/ Matrix System  to store & release the drug at the skin site.

c. Release Liner  removed before application & enables drug release

d. Adhesive layer  to maintain contact w/ the skin after application

e. Protective Peel Strip

Four Layers for Membrane-controlled & Continuous Transdermal System:

1. Backing Layer

2. Drug Reservoir

3. Microporous rate-limiting membrane

4. Adhesive foormulation

Layers of the Transderm-Nitro Transdermal Therapeutic System (Summit):

1. Backing

2. Drug Reservoir

3. Control Membrane

4. Adhesive Layer
5. Protective Peel Strip

Nitro-Dur Transdermal Infusion System:

1. Foil Coverstrip 5. Microporous Tape

2. Drug Matrix 6. Absorbent Pad

3. Release Liner 7. Occlusive Overlay

4. Foil Baseplate

Layers of Two-Layer Transdermal Drug Delivery System:

1. Film Backing

2. Drug/ Adhesive Layer

Examples of TDDSs:

1. Transdermal Scopolamine
for motion sickness, nausea & vomiting
anticholinergic/ antimuscarinic (M1 )
Transdermal Scop
 first TDDS
1979 (Baxter®)
 Ciba® >> Novartis®

2. Transdermal Clonidine first TDDS for Hypertension

3. Transdermal Nitroglycerin for the relief of pain associated w/ angina pectoris

4. Transdermal Nicotine for smoking cessation to prevent withdrawal symptoms & physical
dependence

5. Transdermal Estradiol

hormone replacement therapy:

 -primary ovarian failure

-female hypogonadism

-vasomotor symptoms associated w/ menopause

-atrophic vaginitis

-Kraurosis Vulvae  aka Briesky Disease

6. Transdermal Testosterone

Testoderm®

 only applied at scrotal skin Androderm®

 both the scrotal & at the back of patient

Novel Topical Systems:

1. Iontophoresis (IP)  is an electrochemical method that enhances the transport of some solute
molecules by creating a potential gradients through the skin w/ an applied electrical current or
voltage
 induces increase migration of ionic drugs into the skin by electrostatic repulsion.
 Advantages of IP:
a. Control of the delivery rates by variation of current density, pulsed voltage, drug
concentration, & ionic strength
b. Eliminating gastrointestinal incompatibility, erratic absorption, & first-pass
metabolism
c. Reducing side-effects & variation among patients
d. Avoiding the risks of infection, inflammation, & fibrosis associated w/ continuous
injection or infusion.
e. Enhancing compliance w/ a convenient & non-invasive therapeutic regimen.
Disavantage of IP:
Skin irritation at high current densities (this can be eliminated or minimized by reducing
the current)
Drugs deliver through IP:
Pilocarpine-induce sweating in the diagnosis of cystic fibrosis
Topical: -Fluoride  to the teeth -Dexamethasone
 anti-inflammatory into joints -Lidocaine
 as a topical anesthetic
 Variation affecting IP:
1. Current  can be direct, alternate, or pulsed & can have various waveforms, including square,
sinusoidal, triangular & trapezoidal
2. Physicochemical Variables  include the charge, size, structure & lipophilicity of the drug.
3. Formulation Factors  include drug concentration, pH, ionic strength & viscosity
4. Biologic Factors  pertain to the skin, to which the electrodes are applied, its thickness,
permeability, presence of pores, & so on.
 5. Electroendosmotic Flow  results when a voltage difference is applied across a charges
porous membrane, resulting in a bulk fluid flow in the same direction as the flow of counter
ions.

2. Phonophoresis
 synonyms:
-ultrasound
-sonophoresis
-ultrasonophoresis
-ultraphophoresis
 is the transport of drugs through the skin using ultrasound
 is combination of ultrasound therapy w/ topical drug therapy to achieve therapeutic
drug concentrations at slected sites in the skin.
 used by physiotherapist
Three Effects of Ultrasound:
1. Cavitation  is formation & collapse of very small air bubbles in a liquid in contact w/
ultrasound & waves
2. Microstreaming  closely associated w/ cavitations, result in efficient mixing by inducing
eddies in small-volume elements of a liquid; this may enhance dissolution of suspended drug
particles, resulting in a higher concentration of drug near the skin, for absorption
3. Heat Generation  results from the conversion of ultrasound energy to heat energy & can
occur at the surface of the skin as well as in deeper layer of the skin.
most often drug administered through Phonophoresis:
Hydrocortisone
IV. Liquid Dosage Forms: Single Phase
Solutions
 are liquid preparations, that contain one or more chemical substances dissolved in a
suitable solvent or mixture of mutually miscible solvents
 homogenous one-phase system consisting of 2 or more components
 most commonly used liquid dosage form
Advantages:
(1) Complete homogenous doses
(2) Immediate availability for absorption & distribution
(3) Provides a flexible dosage form -easy to swallow
-can be used by any route of administration
-easy to adjust dose
General Rules in Preparing Solution:
1. Know the solubility characteristics of the drug or chemical
2. Choose the proper solvent
3. The salt form of the drug is used
4. When adding salt to syrup, dissolve in a few mL of water then add syrup to volume if an
alcoholic solution of a purely water-soluble drug is used, add the aqueous solution to the
alcoholic solution
Physicochemical: Product of any combination of the three states of matter:
 Solid, Liquid, Gas (S-L, L-L, S-G, L-G)
Pharmaceutical: Liquid Dosage Forms containing active ingredients dissolve in a suitable
solvent or a mixture of mutually miscible solvent.
 Solubility: State when the total amount of solute in the solution & excess particles reaches
Equilibrium.

Descriptive Terms Parts of Solvent needed to dissolve 1 part of

solvent
Very Soluble <1
Freely Soluble 110
Soluble 1030
Sparingly Soluble 30100
Slightly Soluble 1001000
Very Slightly Soluble 100010,000
Insoluble >10,000

Benzocaine Topical anesthetic

Camphorated Parachlorophenol Dental antiinfective.
Carbamide Peroxide Topical Solution Dental antiinfective.
Cetylpyridinium Chloride Solution & Local antiinfective
Cetylpyridinium Chloride Lozenges
Erythrosine Sodium Topical Solution & Diagnostic aid (dental disclosing agent)
Erythrosine Sodium Soluble Tablets
Eugenol: -Dental analgesic
Lidocaine Oral Spray: Topical dental anesthetic
Nystatin Oral Suspension Antifungal
Saliva Substitutes Electrolytes in a carboxymethylcellulose
base
Sodium Fluoride Oral Solution & Sodium Dental caries prophylactic
Fluoride Tablets
Sodium Fluoride And Phosphoric Acid Gel & - Dental caries prophylactic
Sodium Fluoride And Phosphoric Acid Topical
Solution
Zinc Oxide–Eugenol Mixture - Temporary filling mix

Topical Solutions:
1. Aluminum Acetate Topical Solution (Burrows Solution)
 used in dermatologic loton, creams, & pastes
 astringent wash
 after dilution of 10-40 part of water, used as wet dressing

2. Aluminum Subacetate Topical Solution

starting solution for Aluminum Acetate Solution
astringent wash & wet dressing
  Ration of Aluminum Oxide
 HAc:
Al.Sub  1:2:35
Al. Ac  1:13:52
3. Calcium Hydroxide Topical Solution (Limewater; Liquor Calcis)
 composed of not less than 140 mg of Ca(OH)3 in every 100mL of solution
used as astringent
 Preparation: Ca(OH)3 more soluble in cold water
 Dispensing: Dispense the supernatant liquid using a “SIPHON”

4. Coal Tar Topical Solution

composed of 20% coal tar + 5% Polysorbate 80 (solubilizer)
nearly black viscous liquid w/ a sharp burning taste & has naphthalene-like odor.
local antieczema (contact dermatitis)
5. Hydrogen Peroxide Topical Solution (Agua Oxygenada)
Bubbling Effect: release of O2
H2O2 catalase> O2
3%  10 volumes
6%  20 volumes
local anti-infective for use topically on the skin & mucous membrane
6. Povidone-Iodine Topical Solution
complex of I2 + Polyvinylpyrolidone (PVI)
Iodine in Povidone Iodine  10%
surgical scrub & non-irritating antiseptic solution
 1:5000  concentration of Iodine which is effective to combat many common bacteria in
distilled water
7. Thimerosal Topical Solution
water-soluble organic antibacterial use for its bacteriostatic or fungistatic effect
Thimerosal in solution  o.1%
Dispense= 1:5000 concentration
disinfect skin prior to surgery & as a first aid application to wounds & abrasions

Types of Solutions:
Aqueous Solutions:
1. Aromatic Water (Medicated Waters)
 clear, saturated aqueous solutions of volatile oils or other aromatic or volatile
substances.
uses: Perfuming Vehicle
storage: Tight, Light-resistant Bottles
2. Aqueous Acids:
a. Hydracids  do not contain oxygen
b. Oxygen-containing acid
 c. Diluted Acids  aqueous solutions of concentrated acid dissolve in purified water of
suitable strength 10% w/v (except Acetic Acid, 6%)
 Example: Diluted HCl (treatment for Achlorydia/ Hypochlorydia)
 Primary Considerations
 Must be sipped using a straw to protect dental enamel
 Percentage strength of official undiluted acid is expressed in % (w/w)
 Percentage strength of official diluted acids is expressed in % (w/v)
3. Douches  used as cleansing or antiseptic agent directed against a part or into cavity of
the body
 most frequently dispensed in the form of a powder w/ the directions for dissolving in a
specified quantity of warm water
Vaginal Douche
 cleanse the vagina
 mostly has antibiotic (Chlorhexidate Glucorate)
***vagina must be Acidic
4. Enemas  rectal injection employed to evaluate the bowel
Rectal Enema  used to cleanse the bowel in large intestines before & after surgery
 contain in plastic squeeze bottle
 components:
-Na phosphate/Biphosphate
-Docusate Na (Stool Softener)
- Glycerin - Light Mineral Oil
Examples:
Sodium Phosphate Enema
Hydrocortisone Enema
Aminophylline Enema
5. Gargles  for treating the pharynx & nasopharynx
6. Washes  most often used for its deodorant, refreshing or antiseptic effects
7. Juices  are prepared from fresh ripe fruits
8. Sprays  are applied to the mucous membranes of the nose & throat by means of
“Atomizer” or “Nebulizer”  aqueous or oleaginous solutions in the form of coarse
droplets or finely divided solid usually introduce into body cavities especially in
Nasopharyngeal Tract.

Sweet or Other Viscid (Sticky) Aqueous Solutions:

1. Syrups  are concentrated solution of sugar such as sucrose in water.
 Two Types: (a) Medicated  AI
(b) Non-medicated vehicle
 Methods in Syrup Making:
1. Solution w/ the aid of Heat  if we want to produce syrup quickly
2. Solution w/ Agitation w/out the aid of Heat  if we want to prevent sucrose inversion or
caramelization
3. Addition of Sucrose to a flavored or medicated Liquid
 4. Percolation
a. Syrup, NF (Simple Syrup)  nearly saturated aqueous solution of sucrose (85% w/v)
 low solvent capacity for water soluble drugs
 inherently stable & resistant to the growth of microorganisms when properly prepared &
maintained
b. Cherry Syrup  if the drug material requires an acid medium
c. Cocoa Syrup  if the drug is Bitter tasting
d. Orange Syrup  if the drug is stable in acid medium
e. Raspberry Syrup  disguise the sour or salty taste of saline medicaments
f. Ora-sweet or Ora-sweet SF (Sugar Free)  for extemporaneous compounding of syrups

2. Honeys  are thick liquid preparations somewhat allied to the syrups

Oxymel  mixture of Honey & Acetic Acid
3. Mucilages  are thick, viscid, adhesive liquids by dispensing gum in water.
4. Jellies  are class of gels in which the structural coherent matrix contains a high portion of
liquid, usually water

Nonaqueous Solutions:
1. Alcoholic or Hydroalcoholc Solutions:

a) Tinctures  from vegetable materials or form chemical substances

 alcohol content: 15-80%
Preparations: Maceration
Percolation
 Examples:
- Iodine Ticture
- Paregoric, USP  camphorated opium tincture
- Opium Tincture, USP  (Laudanum)

b) Elixirs  are clear, pleasantly flavored, sweetened hydroalcoholic liquids intended

oral use.
 alcohol content:5-40%,but most of the time,varies widely
Methods: Solution w/ Agitation; Admixtures of Solution
 Two types of Elixirs:
-Non-medicated  vehicle
-Medicated  Antihistamine ;Digoxin; Barbiturates
 Examples:
- Aromatic Elixir, NF  22% alcohol
Preparation: Always add aqueous solution to alcoholic solution.
c) Spirits (Essences)  are alcoholic solution of volatile substances prepared usually by
simple solution or by admixture of the ingredients
 may be taken orally, applied externally, or used by inhalation
 alcohol Content: >60% alcohol
  Methods: Simple Solution Solution w/ maceration ;Distillation
2.Ethereal Solutions
a. Collodions  a liquid preparations containing pyroxylin in a mixture of ethyl ether &
ethanol
 is prepared by dissolving pyroxillin (4%) in a 3:1 mixture of ether & alcohol.
 Salicylic Acid Collodions
 keratolytic in the treatment of corns & warts
 Collodion, USP / Flexible Collodions
 water-repellant protective for minor cuts & scratches.
Flexible Collodions  10% of Salicylic Acid + 3% Castor Oil (for
flexibility) 2% Camphor (for water-proofing)

Pyroxylin  aka Soluble Guncotton

Nitocellulose
Collodion Cotton
 product of reaction of nitric acid & sulfuric acid on cotton
 is composed chiefly of cellulose tetranitrate
 harsh to touch& extremely flammable
moisten by 30% alcohol
 4% of Pyroxylin (in collodion), dissolve in 3:1 ratio of ether & alcohol

3. Glycrin Solution  valuable pharmaceutical solvent forming permanent & concentrate

solutions
a. Glycerites  are solutions or mixture of medicinal substances in Not Less Than
50%Glycerin
 are hygroscopic & should be stored in tightly closed containers

4. Oleaginous Solutions
a. Liniments (Embrocations)  applied w/ friction or by rubbing
 alcoholic or Oleaginous solutions containing mpre than one medicinal agent intended
to be rubbed on the skin
 CI: Broken Skin or Bruise Skin
 Label “For external use Only”
 Two types:
Alcoholic Liniment
Oleaginous Liniment

b. Oleovitamins  are fish liver oils diluted w/ edible vegetable oil of solutions of the
indicated vitamins
c. Toothache Drops  for temporary relief of toothache
5. Medicated Solutions for Vaporization
a. Inhalations  are drugs or solution of drugs administered by the nasal or respirator route
for local or systemic effect
b. Inhalations (Insufflations)  consist of finely powdered or liquid drugs that are carried into
the respiratory passage by the use of special delivery system.
c. Inhalants  drugs or combination of drugs which by virtue of their high vapor pressure, can
be carried by an air current into the nasal passage where they exert effect.
 Examples:
- Aromatic Elixir, NF
 22% alcohol

Other Solutions:
a. Nasal Solutions  aqueous solutions designed to be administered to the nasal passages in
the form of drops or sprays
Ephedrine  nasal decongestant (vasoconstrictor)
Lypressin  for diabetes

b. Otic or Aural Solutions  aqueous solutions designed to be administered t.o the ear

c. Irrigation Solution  aqueous solutions used to wash or bathe surgical incisions, wounds, or
other body tissue