MANUF LAB - Semisolids

Medicated application

They are generally referred to as therapeutic ointments, creams, pastes, and other forms of viscous consistency intended for external application onto the skin

Cosmetic, Therapeutic

Semi-solids can be used in _______ purpose or __________ purpose

As vehicles for topically applied drugs; As emollients (provides soothing of softening effect on the surface tissues); As protective or occlusive dressing on the skin

Uses of Medicated applications (3)

Emollients

It is the term used when a topical preparation provide soothing / softening effects on the surface tissues

Non-medicated

(Medicated/non-medicated) ointment bases are commonly used as vehicles for topically applied drugs

Partition coefficient of the drug substance; Moisture and temperature in the environment of the skin; Pathological injury to the skin

Factors influencing absorption of drugs through skin

Partition coefficient of the drug substance

[Factors influencing absorption of drugs through skin] Substances possessing both water and lipid solubility are favorably absorbed through the skin

natural moisturizing factor

[Factors influencing absorption of drugs through skin] The moisture balance in the stratum corneum layer of the epidermis is due to the presence of a combination of compounds known as the ________________

Sebaceous glands

These glands are the ones responsible for secreting oil on our skin

Fat

[Factors influencing absorption of drugs through skin] These compounds (stated in moisture and temperature) claim that the _______ on the human skin provides a protective film, to prevent this factor from being stripped from the skin during excessive contact with water, as in bathing.

Insensible perspiration

[Factors influencing absorption of drugs through skin] The skin constantly releases water in the skin surface, which evaporates quickly, without being noticed. This is called ____________________

Aspirin

[Factors influencing absorption of drugs through skin] There are drug substances which penetrate faster, when the temperature of the environment is higher. One such example is ___________

Pathological injury to the skin

[Factors influencing absorption of drugs through skin] Skin penetration has been enhanced by abrasions or when the skin is tripped of its barrier layer

Dermis layer

[Factors influencing absorption of drugs through skin]What layer of the skin is affected of its barrier layer when there is pathological injury to the skin

semisolid base

Penetration of drug substances may be enhanced by the use of a suitable __________ base. The vehicle may help increase the rate of penetration of drug substance into the skin and serves as a carrier for the API

The FDA

The ______________ approves chemical substances and states the maximum concentration considered safe for food and cosmetics.

Brochures

The supplier of the drug substances supplies _____________ which indicates the FDA approval safety tests are made

Sensitization

Perfumes are not generally included in the formulation of medicated semi-solid, because many dermatologists object to the use due to the danger of _____________

Hydrocarbons; Hydrocarbon waxes; Oleaginous substances; Fatty acids and alcohols; Polyols, insoluble powders

Frequent starting materials in semisolid preparation (6)

Petrolatum and Mineral Oil

[Frequent Starting Materials] These are the most widely used substances in semisolids, next to water

Petrolatum

[Frequent Starting Materials] A complex mixture of semisolids containing hydrocarbon aliphatic, cyclic, saturated, unsaturated, branched and unbranched substances in varying proportions

Mineral oil

[Frequent Starting Materials] It is derived from petroleum acid, it is less tacky and with lower viscosity

Hydrocarbon waxes

[Frequent Starting Materials] They help increase the viscosity of hydrocarbons such as petrolatum and mineral oil.

Hydrocarbon waxes

[Frequent Starting Materials] Prevent separation of hydrocarbons from the ointment

Paraffin, beeswax, ceresin wax (mixture of paraffin and ozokerite)

[Frequent Starting Materials] Examples of hydrocarbon waxes

Oleaginous substances

[Frequent Starting Materials] Vegetable fixed oils which contain glycerides of mixtures of saturated and unsaturated fatty acids (MCT's and FA's)

Emollient and skin-lubricating effects

[Frequent Starting Materials] Oleaginous substances are employed for its ______ and _________ effects

Fixed oils of peanut, olive, sesame, cottonseed, coconut, corn

[Frequent Starting Materials] Exampels of oleaginous susbstances

Fatty acids and alcohols

[Frequent Starting Materials] They function as auxiliary emulsifiers and viscosity-builders

Stearic acid and Stearyl/Cetyl alcohols

[Frequent Starting Materials] Examples of fatty acids and alcohols (2)

Stearic acid

[Frequent Starting Materials] Fatty acids used as emulsifiers in water-removable creams

Stearyl/Cetyl alcohols

[Frequent Starting Materials] Alcohols used as emollients, and provide the necessary firmness/softness in consistency of creams

Emulsifiers

[Frequent Starting Materials] Substances that prevent coalescence and act as product stabilizers

Triethanolamine stearate, SPANS, TWEENS, CARBOWAX

[Frequent Starting Materials] Examples of emulsifiers (4)

Polyols

[Frequent Starting Materials] These are used as humectants, prevents dehydration and "crusting" on top of creams and ointments in jar

Glycerin, PG, Sorbitol 70%; PEG (lower MW)

[Frequent Starting Materials] Examples of polyols (4)

Insoluble solids

[Frequent Starting Materials] These must be uniformly dispersed throughout the semisolid vehicle to assure product homogeneity

Impalpable

[Frequent Starting Materials] Solids in the insoluble powders must be ___________ or soft to the touch

74 microns

[Frequent Starting Materials] particles less than _________ microns (equivalent to 200 mesh) is said to be impalpable to most people

Nature of the skin lesion; skin type,; solubility of the formulation of components; stability of the APIs

Factors influencing the choice of semi-solid vehicles (4)

Hydrocarbon bases

Classes of semi-solid vehicles / bases recognized in the USP

Hydrocarbon bases

[Classes of Bases] Typically lipophilic, spreads easily onto the skin, difficult to remove/wash off

Hydrocarbon bases

[Classes of Bases] They act as occlusive dressings, since the normal evaporation of insensible perspiration is inhibited

White petrolatum, mineral oil, white/yellow ointment USP

Examples of Hydrocarbon bases

Absorption emulsifiable bases

[Classes of Bases] These are hydrophilic mixtures formed by the additions of substances that possess polar groupings (sulfates, carboxyl, hydroxyl or ether linkages) to a Hydrocarbon Base

Lanolin, cholesterol, sorbitan monostearate/monooleate

[Classes of Bases] Absorption emulsifiable bases, such as _______________ (3) are added to hydrocarbon bases to make it HYDROPHILIC

W/O

[Classes of Bases] Type of emulsion of absorption bases

Water-removable / Washable bases

[Classes of Bases] These are O/W emulsions referred to as Creams; Upon application, there is little or no evidence of its presence onto the skin

Creams

[Classes of Bases] Water removable bases are also referred to as __________

Water-removable / Washable bases

[Classes of Bases] Best for moist skin lesions, since its O/W character ten to adsorb serous discharges

Vanishing creams, foundation creams, shaving creams, hand cream

[Classes of Bases] Examples of Water-Removable bases (Creams) (4)

Water-removable / Washable bases

[Classes of Bases] Vanishing cream, hand cream, foundation cream, and shaving cream belong to this category because upon application and rubbing in to the skin, there is little or no visible evidence of its presence

Water-soluble / greaseless bases

[Classes of Bases] Prepared from mixtures of high and low MW PEG

Water-soluble / greaseless bases

[Classes of Bases] No water is required in its preparation

Ether

[Classes of Bases] Greaseless bases are water soluble due to many polar groups and _________ linkages

Water-soluble / greaseless bases

[Classes of Bases] Suitable combinations of high and low MW PEG yield products having an ointment-like consistency, which soften or melt when applied topically

Liquids

[Classes of Bases] In greaseless bases, when Low MW PEG are used, it forms __________

Unctuous

[Classes of Bases] In greaseless bases, when Moderately high MW PEG are used, it forms ________ preparations

Solids

[Classes of Bases] In greaseless bases, when very high MW PEG are used, it forms ____________

Petroleum jelly, Absorption base (Lanolin or Lanolin Alcohol); Water-soluble base

[Ophthalmic ointments] Semisolid ophthalmic vehicles frequently contain any of the following bases that have been sterilized (3)

Impalpability

[Ophthalmic ointments] Insoluble API powders should meet the requirements for ____________

Sterile and Isotonic

[Ophthalmic ointments] Ophthalmic ointments should be rendered _____ and _______

Gamma radiation or sterilization by filtration

[Ophthalmic ointments] Other ointment base of ophthalmic products: Lanolin sterilized by _____________ or sterilization by _____________

[Ophthalmic ointments] Other ointment base of ophthalmic products: Lanolin alcohol possess _________ properties suitable for eye ointment formulation

Preservatives

These are added to prevent contamination, deterioration, and spoilage by bacteria and molds

stability (with regard to formulation components); container to be used

The chemical preservative for semisolids should be evaluated as to (2)

Boric acid

This preservative may be used in ophthalmic ointments against bacterial/fungal contamination

Water supply, raw materials, pipelines, filling equipment, and containers

Bacterial counts should be made on the __________________ (5)

Unsaturated fatty acids

oxidation happens in (saturated/unsaturated) fatty acids

Antioxidants

These are added to semi-solids whenever oxidative deterioration is anticipated

BHA, BHT, and propyl gallate

Examples of antioxidants used in semi-solids (3)

Toxicity/irritating potency; compatibility; odor; discoloration; solubility; stability

The choice of anti-oxidant is made upon consideration of the following factors (6)

Rigid and strict production procedure; dedicated equipment used for the same product; monitored temperature; unchanged order of mixing

Batch-to-batch uniformity is achieved through _____________ (4)

Fusion method

Anhydrous ointments are manufactured by this process, which is made by dissolving the APIs in the previously melted fats and waxes

Fusion method

The melted mass must be mixed while cooling to ensure the homogenous distribution of the ingredients

Time of mixing; Temperature of mixing; Rate of agitation (and other mechanical works)

Factors to be controlled during the fusion method

Water Phase Vessel/Oil or Wax Phase Vessel - Manufacturing/Mixing vessel - Homogenizer - Storage vessel - Filliing Machine

Steps of manufacturing semisolids (5)

Preparation of the Oil Phase; Hydration of the ingredients in the aqueous phase; Foaming the emulsion; Dispersion of the active/s

Steps in fusion method (4)

70-75 deg C

Temperature

Mineral oil or silicone oil

[Steps in Fusion Method] During preparation of oil phase, dry ingredients are pulverized, blended in advance, and dispersed in ________ or _________

Emulsifiers, stabilizers, thickening agents

[Steps in Fusion Method] During Step 2, ________, _______, and _________ are dispersed water in a separate vessel. This is usually followed by a filtration procedure, if needed. Heating may be required to accelerate hydration.

30-40 deg C

[Steps in Fusion Method] During step 3. The aqueous and oil phases are blended under vigorous agitation to form the emulsion. Temperature is controlled between _________ to _________ deg C.

Defoaming procedures

[Steps in Fusion Method] After step 3, __________ procedures are done to minimize foam formation after the product has emulsified.

Step 4: Dispersion of the active/s

[Steps in Fusion Method] In this step, the APIs are efficiently dispersed to maximize yield and product effectiveness.

Blow fill seal, form fill seal, (di ko alam yung isa)

Methods of filling ophthalmic ointments

Well-closed container; opaque or light resistant; keep in cool place (8-15 deg C)

Storage requirements for semi-solids

Staphylococcus aureus; pseudomonas aeruginosa

[Evaluation of Medicated Applications] Microbial Screening (microbial limit tests) uses these two bacteria for testing

Minimum Fill

[Evaluation of Medicated Applications] This is the assessment of the content uniformity of semi-solids

NLT 90% of the labeled amount

[Evaluation of Medicated Applications] Minimum fill of product weighing 60 g or mL

NLT 95% of the labeled amount

[Evaluation of Medicated Applications] Minimum fill of product weighing 60 g or mL to 150 g or mL

Quantitative assay of % Purity or % Content [Evaluation of Medicated Applications] Standard assays of the APIs

Membrane Filtration Technique and Test Tube inoculation Method

[Evaluation of Medicated Applications] Sterility Tests (2)

Antifungals; Antivirals; Corticosteroids; Antibiotics; Topicals for Vaginal Use

[Evaluation of Medicated Applications] In vivo BA/BE - dermatopharmacokinetic studies (DPS) is applicable to semisolids that contain (5)

Tape stripping

This is used to check for allergic reactions

Otic use; ophthalmic use; that damage the stratum corneum of the skin

[Evaluation of Medicated Applications] In vivo BA/BE - dermatopharmacokinetic studies (DPS) is NOT applicable to semisolids for _____________ (3)

In vivo BA/BE - dermatopharmacokinetic studies (DPS)

[Evaluation of Medicated Applications] This test involves the measurement of: (1) drug concentration in the stratum corneum, (2) drug uptake, (3) apparent steady state, and (4) elimination after drug application onto the skin

pH, Water Content, Foreign Substances, Homogeneity, Metal Particle Detection Test, Leaker Test

Evaluation of medicated applications as per NON-USP requirements (6)

Karl Fisher Method

[Evaluation of medicated applications as per NON-USP requirements] Method used for testing Water content

Physical, chemical, and microbial stability

[Evaluation of medicated applications as per NON-USP requirements] Stability affected by water content (3)

0.5 to 1%

[Evaluation of medicated applications as per NON-USP requirements] Usual water limit