Pharmaceutics Exam 2

ointment

semi-solid preparation intended for external application

- Medicated = those with medicaments for treatment of cutaneous

- non-medicated = ointment bases (used for vehicles in medicated ointments or for their lubricating effects)

What are the purpose of ointment bases?

- emollient or lubricating agent - to make skin soft and more pliable

- Protective barriers- serve as physical barrier

- vehicles in the preparation of medicated ointments

Types of ointment bases - hydrocarbon (oleaginous) bases

- hydrates skin due to sweat accumulation

- occlusive dressing

- difficult to wash off/ remove

- small amount of water can be incorporated into it with difficulty ad can be protective to water labile drugs

- greasy

Hydrocarbon bases - petrolatum

mixture of semisolid hydrocarbons obtained form petroleum

- melting point 38-60 degrees C

Hydrocarbon bases - yellow ointment

USP 95% petrolatum and 5% yellow wax

Hydrocarbon bases - white ointment

95% white petrolatum and 5% white wax

oleaginous bases (suppositories) - paraffin

purified mixture of solid hydrocarbons obtained from petroleum- used to stiffen semisolid ointment bases

oleaginous bases (suppositories) - mineral oil

- mixture of liquid hydrocarbons obtained from petroleum - levigating agent

Types of ointment bases - absorption bases

- those that permit the incorporation of aqueous solutions to become water in oil emulsions

Emollient, occulsive, absorbs water, greasy

- Are already water in oil emulsions which have the ability to absorb additional water

emollient, occlusive, contains water and can absorb additional,

greasy

Types of ointment bases -Water removable bases

- water washable, easier to remove

- non/less greasy

- can be diluted with water

- non/less occlusive

- better cosmetic appearance

- better compliance

Types of ointment bases -Water soluble bases

- contain only water-soluble substances a=

- water removable

- greaseless

- less occlusive

- EX: PEG ointment

What are the ideal properties of an ointment base?

- non-irritating, non-dehydrating, non-greasy

- compatible with common medicaments

- stable

- easily removable with water

- should have good absorptive properties

- good release properties of the drug from the base

Preparation of ointments - mechanical incorporation

- involves both solid and liquid incorporation

- Spatula with a long, broad blade should be used

- insoluble substances should be powdered finely in mortar and pestle and mixed with equal amount of base

- levigation of powders into small portion bases should include levigating agents

mineral oil for oily bases

glycerin for water is the external phase

Preparation of ointments - fusion

- used when the base contains solids that have higher melting points

- the oil phase should be melted separately

- ingredients in the water phase are combined and heated separately to temp equal or above oil phase

- the two phases are combined

- volatile materials are added after the melted mixture cools to desired temp

What are the test requirements for ointments?

- microbial content (must contain preservatives)

- Minimum fill test

- Packaging, storage, and labeling (Metal, plastic tubes, jar)

- examine viscosity and in-vitro drug release

Creams

- semisolid emulsion systems with a creamy white appearance

- intended to be applied to the skin or certain mucous membranes for protective, therapeutic, or prophylactic purposes

Types of creams - oil in water creams

- foundation creams

- hand creams

- shaving creams

pleasing appearence, good feeling after application, non greasy and washable, suitable for oozing wounds

Types of creams - water in oil creams

- cold creams

- emollient creams

Ointment vs creams

- ointment contains 80% oil and 20% water whereas creams are usually 50:50

- ointments are greasier in nature and have thicker consistency (difficult to spread over large areas)

- creams are lighter in consistency and work better across larger areas

- Creams are absorbed into the skin and ointments stay on the skin longer

- Ointments - prescribed for dry skin

- creams - prescribed for oily, moist skin

Pastes

- ointment like preparations into which high percentages of insoluble solids have been incorporated (as high as 50%)

- Usually stiffer (due to presence of solids), less greasy, and more absorptive then ointments

- Starch, zinc oxide, calcium carbonate

Gels

- semi-solid jelly like material that can have properties ranging from soft and weak to hard and tough

- crosslinked system, which may exhibit no flow at rest

Types of gels - hydrogels

network of polymer chains that are hydrophilic and water is usually the dispersion medium

- flexible due to significant water content

Types of gels - organogels

- composed of a liquid organic phase entrapped in a 3-D cross linked network

When are lotions generally used?

- Applied to areas where friction may occur, between the thighs or under the armpits

Advantages of semisolid dosage forms?

- demonstrated ability to readily incorporate a wide variety of hydrophilic and hydrophobic drugs

- reduce undesirable effects arising from the presystemic metabolism

- minimize unnecessary fluctuation in drug concentration

- topical delivery

Classification of dosage forms - tier 1

- route of administration

- gastro-intestinal

- by injection

- mucosal

- topical dermal

- inhalation

Classification of dosage forms - tier 2

- form and physical properties

- aerosols, capsules, gels, lozenges, pellets

Classification of dosage forms - tier 3

- type of release pattern

- immediate, extended, delayed

chemical stability

- expiration date of commercial products and beyond use date of compounded products

physical stability

- reversible on shaking

Performance over time

- in vitro release, disintegration, dissolution

USP - aerosol

- preparations packaged under pressure and contain therapeutic agents and a propellant that are release upon actuation of a valve system

USP - capsules

solid dosage forms in which the API and excipients are enclosed within a soluble container or shell

USP - inhalation powders

- mixture of API and typically carrier, and all formulation components exist in a finely divided state packaged in a suitable container-closure system

USP - creams

semi-solid emulsion dosage form and contain more than 20% of water and volatiles less than 50%

USP - lotions

emulsified liquid dosage form generally intended for external application to skin

- more fluid than semisolid

USP - foams

emulsions containing a dispersed phase of gas bubbles in a liquid continuous phase containing API

- packaged in pressurized containers or special dispensing devices

USP - medical gases

products that are administered directly as a gas

USP - gels

semisolids consisting of either suspensions of small inorganic particles or of organic molecules interpenetrated by a liquid

USP - granules

solid dosage form that are composed of agglomerations of smaller particles

USP - medicated gums

semisolid confection that is designed to be chewed rather than swallowed

- release API into saliva

USP - implants

- long acting dosage forms that provide continuous release of the API often for periods of months to years

USP - inserts

solid dosage forms that are inserted into a naturally occurring body cavity other than rectum or mouth

USP - lozenges

solid oral dosage form that are designed to dissolve or disintegrate slowly in the mouth

USP - ointment

semisolid preparations intended for external application to the skin and contain less than 20% water

USP - pastes

- semisolid preparations of stiff consistency and contain high percentage of finely dispersed solids

USP - transdermal system

discrete dosage forms that are designed to deliver the API through intact skin to systemic circulation

USP - pellets

dosage forms composed of small, solid particles of uniform shape

USP - plasters

semisolid substance for external application and usually supplied on a support material

USP - powders

solid or mixture of solids in a finely divided state intended for internal or external use

USP- medicated soaps or shampoos

solid or liquid preparations intended for topical application to the skin or scalp followed by subsequent rinsing with water

USP - suppositories

- dosage forms adapted for application into the rectum

- usually melt, soften, or dissolve at body temperature

USP - suspension

biphasic preparation consisting of solid particles dispersed through a liquid phase

USP - tapes

- suitable for delivering API to the skin

- consists of an API impregnated into a durable yet flexible woven fabric or extruded synthetic material that is coated with an adhesive agent

Components of USP 1163 (quality assurance) - Training and standard operating procedures

- Personnel involved in nonsterile or sterile compounding require additional specific training and periodic retraining

- SOP for pharmaceutical compounding = documents that describe how to perform routine and expected tasks in compounding environment

beyond use dating, chemical and physical stability, compounding methods, dispensing

Components of USP 1163 (quality assurance) - documentation

- to provide a record of all aspects of compounding operations and procedures

Components of USP 1163 (quality assurance) - verification

- involved authoritatively signed assurance and documentation that a process, procedure, or piece of equipment is functioning properly and producing expected results

- checking to ensure calculations, weighing and measuring, order of mixing

Components of USP 1163 (quality assurance) - testing

- Included during the compounding process and of the finished compounded preparations

- should know the importance of testing, when to test, what to test, what appropriate methods, the limits of the test

Components of USP 1163 (quality assurance) - cleaning, disinfecting, and safety and who does this apply to?

applied to both equipment and facilities

Components of USP 1163 (quality assurance) - containers, packaging, repackaging, labeling, and storage

glass, plastic, closures for injections, good packaging practices,

Components of USP 1163 (quality assurance) - outsourcing

documentation on file for all BUDs

Components of USP 1163 (quality assurance) - responsible personnel

in quality assurance program are essential in assuring safety, identity, strength, quality, and purity of compounded drug preparations

Validation of compendial procedures (USP 1225) - accuracy

- closeness of test results obtained by that procedure to the true value

- should be established across its range

Validation of compendial procedures (USP 1225) - precision

- degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of homogenous sampe

- expressed as standard deviation or relative standard deviation of a series of measurement

Validation of compendial procedures (USP 1225) - specificity

- ability to asses the analyte in the presence of components that may be expected to be present such as impurities, degradation products

- Identification test - ensure identity of analyte

- Purity test - accurate estimation of the content of impurities

- assays - accurate estimation of the content or potency of the analyte

Validation of compendial procedures (USP 1225) - detection limits

- Lowest amount of analyte in a sample that can be detected but not necessarily quantitated under the stated experimental conditions

- usually expressed as the concentration

Validation of compendial procedures (USP 1225) - quantitation limits

- lowest amount of analyte in a sample that can be determined with acceptable accuracy and precision as set in the test

Validation of compendial procedures (USP 1225) - linearity

- ability to elicit test results that are directly or by a well defined mathematical transformation proportional to the concentration of analyte in samples within a given range

Validation of compendial procedures (USP 1225) - range

- interval between the upper and lower levels of analyte that have been demonstrated to be determined with a suitable level of precision, accuracy, and linearity

Validation of compendial procedures (USP 1225) - robustness

measure of its capacity to remain unaffected by small but deliberate variation in procedural parameters listed in the procedure documentation and provides an indication of its suitability during normal range

Categories for validation - category 1

- analytical procedures for quantitation of major components of bulk substances or active ingredients

Categories for validation - category 2

analytical procedures for determination of impurities in bulk drug substances or degradation compounds

Categories for validation - category 3

analytical procedures for determination of performance characteristics (dissolution, drug release)

Categories for validation - category 4

identification test

Suppositories

solid dosage forms containing medicinal agents intended for insertion into the rectum, vaginal cavity, or urethral tract

- after insertion they usually melt or undergo dissolution to release the drug for pharmacological effect

- local or systemic action

Suppository types - rectal suppositories

- cylindrical with one or both ends tapered

- adult rectal - 2 gram

- infant rectal - 1 gram

types of suppositories - vaginal

- also known as pessaries

- typically weigh 3-5 grams

- oviform or cone shaped

types of suppositories- urethral suppositories

- also known bougies

- pencil shaped

Advantages of suppositories

- the patient is unable to use the oral route due to infection of GIT, nausea, vomiting

- The drug is less suited for oral route due to causing GI side effects, insufficiently stable at pH of GIT

Disadvantages of suppositories

- slow and incomplete absorption

- inter and intra subject variation

- Development of local irritation and inflammation

- long preparation time

- problems with large scale production and suitable shelf life

- demanding stringent storage conditions

properties of an ideal suppository base

- melts at rectal temperature of 37.5 degrees C

- nontoxic and nonirritating to sensitive and inflamed tissues

- convenient to handle by the patient and does not break or melt

- does not leak from the rectum

- stable on storage, does not change color, odor, and drug release pattern

- physically stable and compatible with variety of drugs

- no meta-stable forms

Classifications of suppository bases - oleaginous

- cocoa butter

- yellowish, white solid with an odor of chocolate and is mixture of glyceryl esters of different unsaturated fatty acids

- most widely used and is the base of choice is base is unspecified

- major concern is polymorphism (if overheated produces unstable gamma and alpha crystals), adherence to mold

Classifications of suppository bases - water soluble bases

- do not melt at body temperature but dissolve in the secretion of the body cavity

- glycerinated gelatin

- PEG (molecular weights of 300-600 are clear colorless liquids. Molecular weights of 600-1000 are semisolid)

Manufacturing of suppositories - hand molding

- oldest and simplest method of making suppositories

- Drug and base mixture is triturated thoroughly

- plastic mass formed is rolled into a cylinder on an ointment slab

- divided into equal segments with shape blade

- used when only a few suppositories are to be prepared in a cocoa butter base

Manufacturing of suppositories - compression method

- involves compression using suppository machines

- base and other ingredients are combined

- the friction of the process causes the base to soften into a paste like consistency

- the method requires that the capacity of the molds first be determined by compressing a small amount of the base into the dies and weighing the finished suppositories

Manufacturing of suppositories - pour molding

- most commonly used method

- The material is melted on a steam bath

- active ingredients are added to the molted mass

- the mass is poured into cooled metal/disposable molds

Manufacturing of suppositories - automatic molding

- pouring, cooling, and removal from the mold can be performed by rotary automatic molding machines

Specific problems with suppositories - presence of water

- speeds up the oxidation of fats

- if water evaporates the dissolved substance crystalizes out

- reaction between ingredients is increased

Specific problems with suppositories - hygroscopicity

- glycerinated gelatin suppositories have moisture loss by evaporation in dry climates and absorbs moisture under conditions of high humidity

- PEG bases

Specific problems with suppositories - rancidity and antioxidant

- rancidity results from the autoxidation and subsequent decomposition of unsaturated fats into low and medium molecular weight saturated and unsaturated aldehydes, ketones and acids, which have strong unpleasant odor

Specific problems with suppositories - lubricant or mold adherence

- cocoa butter adheres to suppository mold

- various mold lubricants or release agents must be used to overcome

Specific problems with suppositories - volume contraction

- occurs after cooling

- contraction hole formation at the open end of the mold

- can be eliminated by pouring a mass slightly above its congealing temperature into a mold

Specific problems with suppositories - low viscosities

- can result in the sedimentation of suspended particles

- viscosity is important for its behavior in the rectum after melting

- to overcome use base with a more narrow melting range that is closer to body temp

Pulmonary drug delivery systems

- consists of procedures or device which allows a drug to be administered into the respiratory tract primarily through lungs

types of pulmonary drug delivery systems - therapeutic gases

inhaled anesthetic agents

types of pulmonary drug delivery systems - inhaled aerosols

solid or liquid particles dispersed in gas

- system under pressure

types of pulmonary drug delivery systems - metered dose inhalers

- products that are packaged under pressure and the active ingredient is released upon activation of an appropriate valve system

types of pulmonary drug delivery systems - nebulizers

- continuously produce a dispersed cloud of liquid droplets in air stream

- air jet = high velocity air stream

- ultrasonic = piezoelectric crystal, vibrates under electric field

- vibrating mesh = piezoelectric crystal to a laser drilled metal mesh

types of pulmonary drug delivery systems - dry powder inhalers

- diverse group of portable devices that creates an aerosol of solid particles suspended in air

Advantages of pulmonary drug delivery systems

- facilitates self medication

- may replace injectable products or dosage forms

- a dose can be dispensed from the container without affecting its stability

- medication can be delivered directly into the affected area

- onset of drug response is faster

- bigger absorption area