Pharmaceutical Dosage Form Lab prep 6-18

PHARMACEUTICAL DOSAGE FORMS LAB

REVIEWER

#6 GLYCERIN SUPPOSITORIES

SYNONYM: glycerina LABEL: red label

CONTAINER: suppository bottle

Suppository - solid dosage form intended for insertion into the body orifices where they melt, soften, dissolvem and exert localizied or systemic effect. 5 TYPES OF SUPPOSITORIES

1. rectal - cylindrical or bullet shape - 32 mm (1 ½ inch)

- 2g adult; 1g children Use: glyercin – laxative effect

Sodium stearate – (Soap); solidifying agent

 Cathartic – acts directly on colonic mucosa to produce normal peristalsis. Not appreciably affects the motility of small intestine

 Relieve pruritus ani – pain associated w/ hemorrhoids

 constipation

2. urethral (bougies or inserts) – slender, pencil shaped.

Male: 4g; 140 mm long, 3-6 mm diameter Female: 2g; 60-70 mm long

Use: dilatation of uterus Anti-infective agent Erectile dysfunction Tx of local infection

3. vaginal (pessaries) - globular, oviform, cone-shaped; 5 grams.

Caused by: Trichomonas vaginalis, Candida (Monilia) albicans, Haemophilus vaginalis

 Estrogenic substances (dienestrol) – used to restore the vaginal mucosa to its normal state. Vaginal tablets (vaginal inserts) - easier to manufacture, more stable, and less messy.

 Anti-infective

 w/ homonal substances Tablet lubricant – Magnesium stearate Disintegrating agent - startch

Use: anti-fungal Anti-infective

Contraceptive (w/ spermicide) 4. otic (aural) – pencil-shaped

5. nasal (burginarium) – pencil-shaped CRITERIA FOR SUPPOSITORIES

1. melts at body temperature 2. firm at room temperature 3. yields at clear melt

4. inert and compatible with other agent 5. wetting and emulsifying

6. acid value (<0-2)

7. saponification value (200-245) – if it forms ester 8. non- irritating

9. iodine value (<7) – determines the unsaturation of double bonds (C=C)

TYPES OF SUPPOSITORY BASES 1. tend to melt -

 cocoa butter (theobroma oil) – polymorphic - very good suppository base for rectal,

seldom used in vagina and urethral - tendency to lower melting point - inability to absorb aqueous solution

 witepool – C12 – C18 (no polymorphism)

 wecobee – only suppository base that came from coconut oil

- ↓ PEG – liquid (300, 400, 600) - ↑ PEG – semi-solid

- ↑↑ PEG – solid- wax ( > 1000)- clear colorless liquid METHODS OF PREPARATION

1. hand rolling – mixing and rolling in a pile tile. 2. compression - more elegant in appearnce - very simple’ avoid sedimentation

- not for large manufacturing

- mix -> supp. Compression device -> apply pressure -> cool

3. fusion method

- melting of all ingredients - pour directly to mold - freeze

- wrap in Aluminum foil

#7 COLD CREAM

CATEGORY: cream

SYNONYM: petrolatum rose water ointment

USES: emollient, cleansing cream, ointment base

CONTAINER: 15 g ointment jar

Creams –semisolid preparations containing one or more medicinal agents dissolves or dispersed in either o/w or w/o emulsion or in another type of water-washable base.

 Easily spread and remove than ointment

 Lighter, less viscous

 Impart pseudo-plastic flow when applied 2 TYPES OF CREAMS

1. oil-in-water – vanishing cream (galen’s cerate) Example: shaving cream, hand cream, foundation cream

2. water-in-oil- imparts oily feeling on skin

Example: cold cream (petrolatum rose water ointment), emollient cream

Substitutes for Spermaceti Wax a. cetyl ester wax

b. cethy alcohol

why is almond oil changed ito mineral oil?

 More stable cold cream

 But if almond oil is used, better emollient property

#8 WHITE OINTMENT

SYNONYM: salve, chrisma, unguentum album,

unguentum simplex

USE: protective, emollient, lubricant

CONTAINER: 15 g ointment jar

Ointment

1. medicated- w/ active ingredient

2. non-medicated- ointment bases. Serves as vehicles for application of medicinal substances

 Medicaments are reduced to impalpable powder before incorporation into a base to reduce grittiness and form a very smooth nucleus for a smooth homogeous ointment. METHODS OF PREPARATION

1. fusion

2. mechanical incorporation – performed by trituration in a mortar or on a slab with spatula is a process known as levigation.

 Unguator

4 TYPES OF OINTMENT BASES

1. oleaginous bases – aka hydrocarbon bases

 Have emollient effect after application

 Water insoluble

 Non-washable

 Cannot absorb water

Examples:

a. Petrolatum, USP – good base for insoluble ingredients

ex. vaseline

b. White petrolatum, USP – yellow wax is decolorized ex. White vaseline

c. Yellow Ointment, USP – aka simple ointment;

- yellow wax- purified wax obtained from honeycomb of the bee Apis mellifera d. white ointment USP - white wax (bleached and purified yellow wax)

e. Lanolin derivatives

e. Synthetic esters – constituents of oleaginous

- glyceryl monostearate, butyl stearate, isopropyl lanolate , stearyl alcohol

2. Absorption Bases

 Water insoluble

 Non-washable

 Can absorb water

 Anhydrous

 Oily, occlusive, lacks cosmetic appeal Examples:

a. Hydrophilic petrolatum – w/o emulsifier

b. Aquaphor – has the capacity to absorb up to 3x its weight in water

c. Aquabase –

d. Wool fat (anhydrous lanolin) – from wool of sheep (Ovis aries)

 Higher percentage of cholesterol

 Ability to absorb twice its weight

3. Water-Removable bases – o/w emulsions; aka emulsion bases.

2 types: a. Water in oil

 water insoluble

 non-washable

 can absorb water

 contains water Examples:

 cold cream (petrolatum rose water ointment)  Lanolin (hydrous wool fat)

 Hydrophilic ointment  Vanishing creams b. Oil in water

 water insoluble

 water washable

 can absorb water

 contains water Examples:  Hydrophilic ointment  Velvachol  Unibase  Acid mantle  Dermabase  Vanicream

Humectants – hydrating agent

 Glycerin

 Propylene glycol

 Sorbitol 70% 4. Water Soluble bases

 Water soluble

 Water washable

 Can absorb water

 Anhydrous or hydrous

 All water soluble, no oil phase Examples: polyethylene glycol ointment

Veegum Methods of Preparation:

1. Fusion – heating all ingredients. Let cool and congeal.

2. Mechanical incorporation - performed by trituration in a mortar or on a slab with spatula is a process knwon as levigation.

COMPEDIAL REQUIREMENTS FOR OINTMENTS:

1. Microbial content – test for absence of Staphyloccocus aureus and Pseudomonas aeruginosa.

 Addition of preservatives such as methyparaben, propylparaben,phenols, benzoic acid, sorbic acid, and quarternary ammonium salts

2. Minimum fill – to ensure proper contents compared with labeled amount.

- 30% max (overage) - 10% minimum 3. Packaging, storing, and labeling

Packaging – jar: glass, plastics ( DO NOT POUR WHILE HOT)

- dispensing jars: plastic - tubes: plasitc, tin, aluminum Labeling – protect w/ tape

- Dual labels Storage – store in a cool place

4. Sterility test and metal particles content for ophthalmic ointment

5. non-gritty – non sand-like feeling to be achieved by heavy trituration.

SELECTION OF APPROPRIATE BASE:

 Topical or percutaneous drug absorption

 Release rate

 Occlusion

 Stability of the drug

 Effect of drug on ointment base

 Easy removable

 Characteristics of surface for application

#9 ZINC OXIDE OINTMENT

SYNONYM: Zinc oxide unguentum

USE: Tx and Prevention for diaper rash (protectant) CONTAINER: 10 g ointment jar

Active ingredient: ZnO #10 SULFUR OINTMENT

SYNONYM: Unguentum sulfuris, Unguentum de Azufre USE: Tx for scabies, ketolytic, acne vulgaris

Active ingredient: precipitated sulfur – make a smoother ointment than any other sulfur. Provides greater reactive surfaces.

#11 CINNAMON WATER

USE: flavored vehicle for internal aqueous solution, carminative

DESCRIPTION OF FINAL PRODUCT: clear, saturated solution

CONTAINER: 30 ml narrow amber bottle

#12 CONCENTRATED PEPPERMINT WATER

USE: flavoring vehicle, carminative CONTAINER: 30 ml narrow amber bottle

DESCRIPTION OF FINAL PRODUCT: clear, saturated solution

 Computed by alligation alternate (x method) Aromatic water- clear, aqueous soution saturated with volatile oils or other aromatic or volatile substances.

 Should be free from empyreumatic (smole-like) and other foreign odor.

METHODS OF PREPARATION

1. distillation - most satisfactory methos of preparation but the slowest and most expensive of the 2 methods. Example: Strong Rose Water

Cohobation – process of repeatedly using the distillate to distille with fresh portions of flowers/ plant materials to minimize loss of water soluble components.

Example: Orange or Rose flowers 2. Solution

2a. Direct solution method - prepared by repeatedly shaking and set aside or 12 hours, filtered through wetted filter paper and qs ad.

2b. Alternate solution method – prepared by incorporating the volatile oil with talc or siliceous earth or pulped filter paper, agitate for 10 mins, filtered and qs ad.

Example: concentrated peppermint water

Dispersing agent - ↑ surface of volatile substances ensuring more rapid saturation of water and forms an efficient filter aid for a clearer solution.

#13 CALCIUM HYDROXIDE TOPICAL SOLUTION

DESCRIPTION OF FINAL PRODUCT: clear, colorless solution

SYNONYM: hydrated lime, lime water, liqoud calcis Ca(OH)2 + CO2 → CaCO3 + H2O

CONTAINER: 30 ml narrow mouth flint bottle REMARKS:

 Should be stored in well-filled, tightly stoppered containers to determine the absorption of CO2 and should be kept in the cool place to avoid degradation.

 Best accomplished by the use of a siphon with care not to entrain the residue.

 Prepared by simple solution NOTE: CaOH is more soluble in cold water

#14 STRONG IODINE SOLUTION

CONTAINER: 15 ml narrow amber bottle REMARKS:

 Iodine crystals stains hand and jewelries  1:2950

 Very volatile

 Very reactive to metal – use porcelain or very hard rubber spatula

 Addition of KI to increase solubility

 Prepared by simple solution

#15 MAGNESIUM CITRATE ORAL SOLUTION

SYNONYM: Milk of Magnesia, Ascapate of Magnesia USE: saline cathartic

DESCRIPTION OF FINAL PRODUCT: colorless to slightly yellow clear effervescent liquid having a sweet, aciduloud taste and a lemon flavor.

REMARKS:

NOTE: CaOH is more soluble in cold water

 Is has tendency to deposit a crystalline solid upon standing

 Official MgCo3 – a basic hydrated MgCO3, or a normal hydrated MgCO3

STORAGE: cool place preferably a ref keepping the cork or rubber liner moist and swollen maintaining airtight seal between cap and bottle.

CONTAINER: 120 ml wide mouth flint bottle

Solutions – liquid preparations that contain one or more chemical substances dissolves in a suitable solvent or mixture of mutually miscible substances.

 Homogenous mixture Relative Terms of Solubility

Descriptive term Parts of solvent required for 1 part of solute Very soluble <1

Freely soluble 1-10

Soluble 10-30

Sparingly soluble 30-100 Slightly soluble 100-1000 Very slightly soluble 1000-10,000 Practically insoluble or

insoluble >10,000 METHODS OF PREPARATION (SOLUTIONS)

1. simple solution - by dissolving solute in a suitable solvent.

Example: NaCl soln, Strong Iodine solution, CaOH soln 2. solution by chemical reaction – by reacting two or more solute with each other in a suitable solvent.

Example: Aluminum subacetate soln, Magnesium citrate solution, Sulfurate lime solution

3. solution by distillation – for isolation of volatile oil 4. solution by extraction – drug or pharmaceutical necessities of vegetable or animal origin.

 Aka extractives

a. maceration – submerging solute

 Best used for drugs containing little or no cellular material such as benzoin, aloe and tolu w/c dissolves almost completely in the menstruum.

b. percolation – using percolator

c. digestion – with the aid of gentle heat d. infusion – blanching; + hot water e. decoction – boiling for 15 mins.

#16 SIMPLE SYRUP

SYNONYM: syrupus, sirup, syrup

DESCRIPTION OF FINAL PRODUCT: clear solution of sucrose in purified water

USE: sweetening agent, sweet vehicle and basis for many flavored and medicated syrup

CONTAINER: 60 ml flint bottle Computation:

→ M Soln = D x V

mass solvent = mass soln- mass solute vehicle (Water) - * with the mass solvent PREPARED BY: percolation

REMARKS: loose cotton – permit sucrose light flow freely

Tight cotton – inhibits flow of liquid Filter paper – to prevent holing of sugar

#17 CHOCOLATE SYRUP

USE: flavored vehicle to active medicaments or substance to improve their taste

SYNONYM: Cacao syrup, chocolate fllavored syrup DESCRIPTION OF FINAL PRODUCT: viscous, dark brown syrup with the odor and taste of cocoa

CONTAINER: 15 ml amber bottle PREPAPERED BY: w/ aid of heat

Ingredients:

1. Cocoa powder – flavorant

2. Sucrose – sweetening agent 3. Liquid glucose

4. Glycerin – humectant (hydrating agent), preservative

5. Sodium chloride – taste balancer 6. Vanilin - flavorant

7. Sodium benzoate - preservative 8. Purified water – vehicle

REMARKS:

 Cocoa is NMT 12% non-volatile ether soluble extractives of fats yields syrups having a minimum tendency to separate.

 Sodium benzoate and glycerin are preservatives added to prevent bacterial and mold growth  because of low concentration of sucrose

(not self-preserving)

Syrup – concentrated aqueous solution containing sugar usually sucrose or any sugar substitute.

Polyols (glycerin or sorbitol) – retart crystalliation of sucrose to increase its solubility.

TYPE OF SYRUP:

1. simple syrup – clear, concentrated, sweet, aqueous, hypertonic solution with striations with concentrations of 85% w/v or 65% w/w (sp gr.: 1.313) for self preserving characteristics.

2. flavored/ non-medicated syrup - contains aromatic and pleasantly flavored substances.

Example: chocolate syrup(flavorant), glycyrrhiza syrup (masks bitter taste of alkaloid)

3. medicated syrup – with active ingredient and has therapeutic efect

METHODS OF PREPARATION FOR SYRUP 1. solution without aid of heat

ADVANTAGE: for heat sensitive. Avoids heat induced conversions

DISADVANTAGE: slowest and time consuming method Example: FeSO4

2. solution with aid of heat – for heat stable only ADVANTAGE: fast

DISADVANTAGE: excessive heating will cause inversion of sucrose and form caramelization

 tendency to ferment

 sweeter

 less stable

 prone to microbial growth

Example: acacia syrup, cocoa syrup, syrup USP

3. percolation – a percolator or a column is being used. The fluid rate of liquid(water) is controlled or adjusted to 20 drops/minute using a cotton.

 The percolator will allow the passage of water slowly through the bed of crystalline sucrose and will eventually dissolve the sugar.

Example: Tolu Balsam, Simple syrup

4. addition of sucrose to a medicated liquid – simple admixture of sugar to a prepared medicated liquid usually a fluidextract or a tincture.

 The syrup prepared through this is not self

preserving.

 Prone to microbial growth – low concentration of sucrose.

#18 ACACIA MUCILAGE

SYNONYM: Mucilage of Gum Arabic, Mucilage of Gum Acacia

DESCRIPTION OF FINAL PRODUCT: thick,viscid, adhesive liquid with brown color

USE:

 Demulcent

 Suspending agent

 Excipient in making pills and troches

 Emulsifying agent for cod liver oil and mineral oil emulsion

CONTAINER: 15 ml flint bottle REMARKS:

 benzoic acid – preservative

 must be free from molds or any other indication of decomposition

 it is unstable and prone to decomposition (+preservative)

 SHOULD NEVER BE MADE IN LARGE QUANTITIES!