Semisolid Dosage Forms

Absorption Bases

- absorb water or aqueous solution w/o change in consistency - greasy, difficult to remove - moderately occlusive - non water washable - vehicle for aq. solns & non-hydrolyzable drugs - more useful to inc. hydrophyllic drgs in oleaginous bases

Topical: Systemic Effects

- applied on the skin - treat systemic conditions - percutaneous absorption occur - transdermal products

Topical: Local Effects

- applied to the skin - treat skin conditions - known as topical dermatological products

Topical: Advantages

- avoid hepatic first-pass metabolism and gastrointestinal incompatibility of drugs incompatibility of drugs - enhanced therapeutic efficacy/minimum side effects - improve patient compliance - abrupt termination of drug effect by wiping the drug off the skin - allows high local concentration

Ointment - Preparation

- based on the nature of ingredients, two methods can be used: * inc method * fusion method

Topical: Disadvantages

- cause irritation - systemic drug absorption may cause side effects - may wipe away easily

Jelly

- coherent material ir rich in liquid - transparent non greasy

Ideal Properties of Bases

- compatible with skin pH and drug substances - inert, non-irritating and non-sensitizing - good emulsifying properties - emollient, protective and easily removable - excellent and desirable drug release properties - pharmaceutically elegant - good stability properties

Water- Soluble Bases

- completely water washable & greaseless - do not contain oleaginous bases - softens w/addition of water * large amts of aqueous solns cannot be effectively inc. - mostly used to inc solid substance - no occlusiveness - PEG Ointment, USP * 60:40 of PEG 400 and PEG 3350 * non-volatile, non-hydrolyzable

Why semisolids?

- consistency between solid and a liquid - retain their shape until a force is applied - easily deformed - 3D structure gives a solid-like character - can be medicated or non-medicated

Hydrophilic Petrolatum, USP

- contain cholesterol, stearyl alcohol, & white wax in white petrolatum - used as propective - Aquaphor a variation of hydrophilic petrolatum

Pastes

- contain high % of insoluble solids (50% or more) - prepared by levigation by inc. solids into a congealed system - good adhesion on skin and less greasy - stiffer than ointments * allows pastes to remain in place after application and absorb serous secretions Ex. Zinc oxide paste, contains 25% ZnO in starch & white petrolatum

Minimum Fill

- dermination of net fill or volume of the contents of filled containers - to ensure proper contents as compared to the label - done by quantitative weighing contents of 10 randomly selected containers * the avg net content of the 10 containers is not less than the labeled amt, and the net content of any single container is not less than 90% of the labeled amt where the labeled amt is 60 g or 60 ml or less * or not less than 95% of the labeled amt where the content is 60g or mL- 150 g/ or ml

Selection of Ointment Bases

- desired release rate of drugs - desirability of topical versus percutaneous drug absorption - affinity to the skin - ability to act as moisture barrier - stability of he drug in the ointment base - condition of the skin - surface to apply the ointments * Scale skin * oozing surface * body cavities

Anhydrous Bases

- do not contain water allow inc. of considerable amt of aq. solns - w/o emulsion on adding water - hydrophilic petrolatum

Application Properties Ideal SSDF

- high aqueous washability - easily applicable - efficient spreading - efficient drug release

Ointments

- homogenous, translucents, viscous, semisolid preparations intended for external applications - hydrocarbon (C16- C30) based semisolids - may be medicated or non-medicated *non-medicated ointments used for protective & lubricating effects - applied to skin or mucous membranes - 2 main formulation components * drug * ointment base

Oleaginous Base

- hydrocarbon base - most hydrophobic base, very greasy, stain clothing and difficult to remove - anhydrous and easily spread on the skin - remain on the skin for long periods w/o drying out - highly occlusive, increase hydration of skin - emollient - very difficult to incorporate water and aqueous preparations - levigating agents should be used to incorporate solids - suitable for hydrolyzable drugs

Lanolin

- hydrous wool fat - obtained from wool of sheep - 25-30% water - anhydrous lanolin: less than 0.25% water

Humectants ( Used for )

- incrase the solubility of active ingredients - to elevate its skin preparation - elevate the hydration of the skin

Xerogel

- liquid is removed & the framework of the particles remain in place - swells up in contact of mucous membrane - reduce bleeding - minimize patient discomfort

Incorporation of Solids

- mixing of finely red solids w/ointment base using geometric dilution - using spatula or mortar & pestle * drug is levigated w/a small amt of vehicle or a miscible component of formulation (concentrate) -mineral oil and PEG are used as levigating agents - the concentrate is mixed w/the remaining bases - if all the solid powders soluble in a single solvent, solids can be dissolved in that solvent and added to the ointment base by spatulation or trituration

Ideal Physiological Properties of SSDF

- non irritating - miscible w/skin secretions - low sensitization index - do not alter membrane/skin functionality

Classification of Semisolids

- ointment - creams - pastes - gels & magmas - poultices - plaster - suppositories

Incorporation of Liquids

- ointment base must have the capacity to accept liquid volume * hydrophilic bases - add a small quantity of aqueous soln to the oleaginous base - to include large volume of aq. preparations * mix the aq. soln w/a small amt of hydrophilic base & then mix w/the oleaginous base - water soluble substances can be mixed w/water soluble bases to a certain limit

Emulsion Bases

- permit incorporation of addtnl amt of aq. solutions - hydrophilic - can be diluted w/oils - water-in-oil emulsions - lanolin

Semisolid Dosage Forms

- products intended to be applied on skin (epicutaneous route) and mucous membranes - cling to the skin or mucous membrane for a prolonged period of time to exert their therapeutic benefits * due to plastic rheological behavior

Packing & storing

- semisolid preparations packed in large-mouthed ointment jars * metal & plastic tubes used as well * depending on compatibility of the formulation ingredients * amber jars for light sensitive materials - Must be stored in well closed containers in a cool place * to protect against microbial contamination * to protect against product separation in heat

Gels and Magmas

- semisolid system in which liquid phase is constrained - aqueous colloidal system of hydrated forms of insoluble medication - with a 3D polymetric matrix having a high degree of physical or chemical cross linking - used for medication, lubrication and carrier for spermicidal agents to be used intra vaginally with diaphragm

Incorporation Method

- simple homogenous mixing of the ingredients - ingredients are incorporated in the ointment base * in mortar & pestle (trituration) * an ointment slab/parchment paper ( spatulation) * using an unguator - in Ointment mills * forces coarsely forced ointments through stainless steel or ceramic rollers to produce ointment w/uniform composition and smooth texture - in steel tank w/homogenizer ( large scale )

Ideal Physiochemical Properties of SSDF

- smooth texture - non-deyhydrating - non-gritty - pharmaceutically elegant - non greasy and non staining - non hygroscopic

Plaster

- solid or semisolid adhesive masses spread on backing paper, fabric, moleskin or plastic - adhesive material is a rubber base or synthetic resin - plasters are applied to the skin to provide prolonged contact at the site * afford protection * bring medication in close contact w/skin surface * salicylic acid plasters used on the toes for the removal or corns

Fusion Method

- suitable for ointments containing substances that are difficult to mix by incorporation - allow for some of the components are mixed by melting and cooled w/constant stirring until congealed - components that do not melt, are added to the cool congealing mixture * Heat labile substances added at low temperature - any further additions can be done by levigation - for large scale manufacturing * fusion is carried out in large steam-jacketed kettles - once congealed, oitnment is passes through an ointment mill to ensure uniform mixing

Labeling

- the label should contain information regarding the type of base used in formulation e.g. water soluble or water insoluble - "for external use ONLY" * preparations only for external use - "Store Below 15C" * to avoid separation and degradation

Additional Standards

- to ensure within lot-to-lot uniformity - viscosity - In-vitro release - Texture: feel upon application (grittiness) - particle size distribution - pH, odor, color

Microbial content

- topical formulations need not be sterile * exception of ophthalmic formulation - must meet acceptable microbial standards * microbial limits are stated in USP for each preparation - Must contain appropriate antimicrobial preservatives - dermatological product should be examined fro P. aeruginosa and S. aureus - rectal, urethral, or vaginal product should be tested for yeast molds

Semisolid Dosage Forms (Uses)

- used for topical applications - common sites of application: *skin *Eye *Nose *Vagina *Rectum - Produce local effect - systemic absorption can also occur - use w/car in pregnant women & nursing mothers

Creams

- viscous semisolid emulsion w/an opaque and creamy appearance * bc of the reflection of light - one or more medication may be dispersed - consistency depends on whether W/O or O/W emulsion *lipophilic emulsifier - W/o creams *hydrophilic emulsifier - O/W creams -Elegant drug delivery system ~vanishing cream - an O/W emulsion composed of waterm stearic acid and other oleaginoous components

Absorption Bases ( 2 Types)

1. Anhydrous absorption bases 2. Emulsion absorption bases

Two-Phase gels (magma or milk)

Consist of floccules of small, distinct particles

Single Phase Gels

Gelling agent is uniformly distributed throughout the liquid and no apparent boundaries exist between them

Inc. of solids (Process)

Size reduction -> Levigation -> Mixing w/base -> Spatulation or trituration -> Mixing base to produce final wt-> Homogenization -> Filling

Humectants

- a humectant is a hygroscopic substance - often a molecule w/several hydrophilic groups, most often a OH(hydroxyl) group

Dispensing Semisolids

- "only for external use" - any specific storage conditions - advise the patient about * the discard date * the route of usage * the freq. of usage * the active ingredients * any of the special side effects/adverse reactions

Formulation Components

- Ingredients used in preparation of semi solid dosage form: * active pharmaceutical ingredients * Bases * Preservatives * Humectants * Anti Oxidants * Emulsifier * Gelling agent * permeation enhancer * buffers

Compedial Requirements

- Ointments and other semisolids must meet following USP compendial requirements: * microbial content * minimum fill * packaging, storage and labeling * additional standards

Bases

- One of the most important ingredients in the formulation SSDF - ointments are majorly made up of * Drug & ointment bases - Bases not only carry medications but also control the extent of drug absorption from the dosage form

Oleaginous Bases (Examples)

- Petrolatum, USP - White Petrolatum, USP - Yellow Ointment, USP - White Ointment, USP - Paraffin

Water-Removable Bases

- Water washable - less occlusive than absorption bases - hydrophilic and can be diluted with water - slightly greasy - O/W emulsions * can be easily removed from skin - hydrophilic Ointment, USP * contain oleaginous phase (propylene glycol and water), propyl and methyl paraben, and sodium lauryl sulfate

4 Classes of Ointment Bases ( USP Classification )

1. Oleaginous 2. Absorption - anhydrous absorption bases - emulsion absorption bases 3. Water-soluble 4. Water-removal

Hydrogels (aquagel)

Hydrophilic polymeric gelling agents in water

Organogels

Thermoplastic (thermoreversible) materials containing liquid organic phase ( eg organic solvent, mineral oil, vegetable oil) entrapped in 3Dimensionally cross-linked network of gelling agents

Transdermal Products

drugs pass through the skin and enter the general circulation