module 5 p1

dosage form

Drug products/preparations containing: • Active Pharmaceutical Ingredient (API)/ Drug • Excipients/ Additives/Adjuncts

Dosage Forms

Sieve number

no. of square openings per linear inch

very coarse

sieve no. 8 no. 40 fine no. 60 very fine no. 80

coarse

sieve no. 20

moderately coarse

seive no.40

fine

sieve no.60

very fine

sieve #80

Drug Delivery

process whereby drugs are delivered to their site of action using a minimum amount of drug necessary to provide & maintain therapy. Effect over a certain period of time with minimum toxicity.

Drug Delivery System

 means administering drugs as formulated preparations

formulations which provide a therapeutic amount of drug to the proper site in the body promptly & maintain the desired drug concentration

 products that allow for the uniform release or targeting of drugs into the body

 encompass the drug formulation, interaction among drugs, formulation matrix, the container & the patient

Drug Product

the finished dosage form that contains the active ingredient, generally, but not necessarily, in association with one or more other ingredients

Three Types of Mortar & Pestle:

1)Porcelain

2)Wedgewood

3)Glass

Porcelain

for comminution

soft aggregates/ crystals

Rough inner surface

Wedgewood

FOR CRYSTALS;

rougher surface

Glass

 smooth surface/ non porous

 solution, suspension, & ointment

 used for staining substance

Levigation

forming a paste by the addition of a levigating agent

(ex. mineral oil, glycerin, PEG)

Pulverization by Intervention

addition of volatile substance to a gummy material (ex. camphor + alcohol; I2crystals + ether)

Spatulation

Blending of powders with a spatula on a tile or paper

• Use: small quantities, non-potent drugs, eutectic mixtures

Sifting

• Powders are passed through sifters

• Results in light, fluffy product

• Not for potent substances

Geometric Dilution

addition of an equal volume of diluent to a potent substance placed in a mortar

Tumbling

large containers rotated by a motorized process

 thorough but time-consuming

Bulk Powders

-Oral Powders, Dentifrices,Dusting Powders,Douche Powders,Insufflations,. Trituration

Divided Powders/Chartulae

Types of Powders

Micronization

a method of producing finer drug particles under 10m size.

Oral Powders

• dissolved in water prior to use

. Dentifrices

• used to clean and polish teeth

• contain a soap, mild abrasive and

anticariogenic agent(prevents cavity formation)

. Dusting Powders

locally applied non-toxic powders that have no systemic action by sprinkling or by means of sifter-top containers.

Douche Powders

dissolve in warm water prior to introduction into a body cavity

Insufflations

blown into body cavities using an insufflator

Boric Acid or Sodium Borate

Astringents, for example, potassium, alum, ammonium alum, zinc sulfate

Antimicrobials, for example, oxyquinoline sulfae, povidone iodine

Quaternary Ammonium Compounds, for example, Benxethonium Chloride

Detergents, for example, Sodium Lauryl Sulfate

Oxidizing Agents, for example, Sodium Perborate g. Salts, for example, Sodium Citrate, Sodium Chloride

h. Aromatics, for example, Methol, Thymol, Eucalyptol, Methyl Salicylate, Phenol

Components of Douche Powders:

Trituration

dilutions of potent powdered drugs (10% API)

Divided Powders/Chartulae

dispensed in individual doses usually in folded papers;

block-and-divide method

White Bond Paper

OPAQUE paper with NO MOISTURE resistance

Vegetable Parchment

thin, semi-opaque, moisture resistant paper(LIMITED)

Glassine Paper

GLAZED TRANSPARENT moisture-resistant paper(LIMITED)

Waxed Paper

transparent waterproof paper; suitable for deliquescent and hygroscopic drugs

GRANULES

dry aggregates of powder particles

NORMAL SIEVE no. 4 to 12

TABLET FORMULATION: SIEVE no. 12 to 20

• Flow well compared to powders

• Less tendency to cake or harden

• More stable to humidity

• More easily wetted by liquids

Advantages of Granules over Powder

Hygroscopic

absorb moisture from the air

Deliquescent

absorb moisture from the air to the extent that they liquidify by partially or wholly forming a solution .

e.g. Potassium citrate, sodium nitrate( absorb water and dissolves)

Efflorescent

release water; boom

Example of Efflorescent Substance:

-Citric Acid

-Ferrous Sulphate

-Atropine Sulphate

Compounding of Granules

1. Wet Granulation

2. Dry Granulation

Wet Granulation

addition of granulating fluid or liquid binder

• most common;

Advantages: -Increased Compressibility

-Improved Dissolution

Disadvantage: -Its not applicable to water/ moisture & heat sensitive (ex: Aspirin)

moisten the mass  screen

granulating fluids  H2O

*fluid bed processing  alcohol isopropanol

fluid bed granulation (liquid is sprayed on suspended powders)

wet granulation

Dry Granulation

for moisture-sensitive and heat labile materials

• use compaction/ compression forces

Disadvantage: Messy

Roll Compaction

Slugging

Processes: dry granulation

Roll Compaction

 uses thin sheets

powders are rolled into dense sheets

sheets are granulated using a mechanical granulator

 sieve granules to obtain desired size

Slugging

tablet pressed

 slugging of powders (formation of large tablets called a “slugs”)

slugs are granulated using an appropriate equipment

 sieve the granules to obtain desired size

 poorly formed tablet

Preparation:

• Dry/Fusion Method – binder is 1 mol of H20 in citric acid

• Wet Method – binder is H20 + alcohol

Effervescent Granules

TABLETS

solid dosage forms which are prepared mainly by compression or molding

• uniform content

• less manufacturing cost

• easy to package and ship

• simple to identify

• most stable of all oral dosage form

• tamperproof

Advantages OF TABLETS

• some drugs resist compression

• some drugs that require encapsulation prior to compression

Disadvantages OF TABLETS

Compressed Tablets

• formed by compression

• some are scored

Layered tablets Multiple Compressed Tablets

– formed by compressing 2 or 3 layers of formulation against each other

(ex. Neozep tablet)

Compression coated tablets – Multiple Compressed Tablets

formed by compressing an outer shell around a tablet core

Sugar Coated Tablets – coated with sucrose-based solution

Film Coated Tablets – coated with a thin layer of polymer material

Enteric-Coated Tablets – remain intact in the stomach but disintegrate in the small intestine

Coated Tablets

Chewable Tablets

• chewed first before swallowing

• diluent: mannitol and xylitol

• (ex. Multivitamins, antacids)

Rapidly/ Orally Disintegrating Tablets

• liquefy on the tongue and then the patients swallow the liquid

• (ex. Risperidone, Ondansetron)

. Buccal Tablets

placed in the lining of the cheeks

• disintegrate slowly (4 hours)

• (ex. Progesterone

Sublingual Tablets

placed under the tongue for systemic absorption

• disintegrate rapidly (2-3 minutes)

• (ex. Nitroglycerin, ISDN

Lozenges

solid dosage forms in a hard candy or sugar base that dissolve slowly in mouth for local effect

• (ex. Strepsils® - dicholorobenzyl alcohol + amylmetacresol

Compounding/ Dispensing Tablets

contain a large amount of API used by pharmacists in compounding multiple dosage units

• no longer use

Hypodermic Tablets

• used by physicians to prepare parenteral solutions • no longer use

Types OF LOZENGES

• Troches – compressed lozenges

• Pastilles – molded lozenges

• Lollipops – lozenges on sticks

Molded Tablets/ Tablet Triturate

prepared by moistening powders and then putting on a triturate mold (may be compressed)

• results to cylindrical tablets which are very soluble in water

Gelatin

partial hydrolysis of collagen from the skin/bones of animals

Types OF GELATIN

• Type A – mainly from pork skin; acid processing

• Type B – from bones and animal skins; alkaline processing

Vegetable Capsules

alternative hydroxypropyl methylcellulose (HPMC) or hard starch

Hard Gelatin Capsules

dry-filled or two-piece capsules (cap and body)

• main components: GELATIN, SUGAR, H20

• additives: colorant, opacifying agent (TiO2) + SO2 [0.15%] (to prevent decomposition of gel)

• moisture content: 12-16% • stored at 21-25°C/30-35% RH

capsule sizes

: (increase capsule size = decrease capacity)

• Human – No. 5 (smallest) – No. 000 (largest)

• Veterinary – No 10. – No. 12

OTHER DESIGN HARD GELATIN CAPSULES

PULVULE- TAPERED AT ONE END

SPANSULE- TAPERED AT BOTH ENDS

Soft Gelatin Capsules

one-piece capsules

• used to contains non-aqueous liquids (vitamin e, cod liver oil, digoxin), suspensions, pastes, and dry materials

• main components: gelatin, plasticizer (glycerin, sorbitol) and preservatives against fungi

• moisture content: 6-10%

• no specific sizes

Order of Capsule Shell Manufacturing

Dipping, Spinning, Drying, Stripping, Trimming, Joining

Encapsulation Procedure of Capsules from start to finish

Rectification —> Separation—→Filling—→ Joining——→ Printing———> Banding ——>Ducting & polishing

1. Diluent or Filler

 to produce the proper capsule fill volume

Ex: Lactose, Microcrystalline Cellulose ,Starch

2. Disintegrants

 to assist the breakup & distribution of the capsule’s contents in the stomach

Ex: Pregelatinized Starch Eroscarmellose Sodium starch Glycolate

3. Lubricants or Glidants  to enhance flow properties

Ex: Fumed Silicon Dioxide Magnesium Stearate Calcium Stearate Stearic Acid Talc

4. Surfactant or Surface-Active Ingredients

 to facilitate wetting by the gastrointestinal fluids to overcome problems Ex: Sodium Lauryl Sulfate

Capsule Excipients:

ORAL MODIFIED-RELEASE SOLID DOSAGE FORMS

drug release features are based on time, course and locations

Advantages OF ORAL MODIFIED RELEASE DOSAGE FORMS

• Economic savings

• Avoid patient compliance problems

• Reduce fluctuation in drug level (to prolong therapeutic effect → to reduce dosing frequency)

• Minimize or eliminate side effects

Extended-Release

provides a prompt desired effect followed by a gradual release of remaining amount

• Problem: dose dumping

TYPES OF EXTENDED-RELEASE

• Controlled Release – zero order

Sustained Release – first order

drug release is other than the time of prompt administration

• Ex: enteric-coated

Repeat Actions

contains 2 single doses of a medication

(1st dose → immediate; 2nd dose → delayed)

Targeted Release

• drug release is isolated in a specific body region/ tissue → absorption and action

Colonic Tablets

deliver the drug into the colon without dilution in other regions of GIT

Rectal suppositories

bullet, torpedo, little finger

2 g (adult) 1 g (children)

32 mm (adult) 16 mm (children)

Vaginal (Pessaries)

globular, ovoid, cone

5 g

Indicated for bacterial or fungal infections and HRT • May be in the form of tablet, suppository, and semisolids • Buffered to pH of 4.5

Urethral (Bougies)

pencil-like

4 g (male) 2 g (female)

140 mm (male) 70 mm (female)

Inserted into the urethra after urination

• Ex: Alprostadil micro suppository

Suppository Bases • Criteria

• Inert, non-irritating, and non-sensitizing

• Firm and does not melt at RT

• Dissolves rapidly in the cavity fluid

Cocoa Butter – most common and good base for rectal suppository; solid at 32°C, melts at 34-35°C; exhibits polymorphism (ȣ - least stable [18°C]; α; β’; β – most stable [34.5°C]

• Wecobee – from coconut oil

• Witepsol – lauric acid is the major component; saturated fatty acids (C12-C18)

. Oleaginous Base

Water-Soluble/Miscible Base

• Glycerinated Gelatin – most common base for vaginal suppositories

• Polyethylene Glycol (PEG)

Vaginal Tablets/Inserts

• Ovoid or bullet-shaped tablets inserted into the vagina using a plastic inserter for local effects • contains antimicrobial agents

Implants/Pellets

• long-acting dosage forms that provide continuous release of the drug to the body

• administered parenterally or subcutaneously

• Pellet implants – small, sterile, cylindrical masses

• Levonorgestrel (Norplant ®) – 5 years

• Leuprolide acetate (Viadur®) – prostate cancer 1 year

OINTMENTS

semisolid dosage forms intended for external use

• Uses: • emollient • occlusive • vehicle

Oleaginous/ Hydrocarbon Base

have emollient, occlusive

• greasy, anhydrous, non-water washable

Petrolatum, USP (Yellow Petrolatum, Petroleum Jelly or Vaseline®)

– purified mixture of semisolid hydrocarbon from petroleum

White Petrolatum, USP

bleached or decolorized

Yellow Wax (Beeswax)

wax obtained from the honeycomb of Apis mellifera

White Wax

bleached or decolorized yellow wax/beeswax

Yellow Ointment, USP (Simple Ointment)

yellow petrolatum + yellow wax

White Ointment, USP

– white petrolatum + white wax