Parenteral Drug Forms

• Parenteral drug forms (DF) are called Parenteralia

Parenteralia Types

• Injections (Iniectabilia)
• Infusions (Infusiones)
• Concentrated solutions for dilution of infusions (Concentrata pro infusionibus) require dilution with sterile water for injections (Aqua pro injectione) to form an infusion
• Powders for dissolving injections (Pulveres pro iniectionibus) are mixed with sterile water to create an injection
• Implants (Implantata)

Parenteralia Quality Requirements

• Clarity is necessary for intravenous (IV) administration
• Osmotic pressure needs to be isotonic with blood plasma
• Current acidity (pH) should be isoacidinic or euacidic
• Sterility requires aseptic preparation, bacterial filtration, and sterilization
• Apyrogenicity means being free of external pyrogens

Methods of Parenteral Administration

• Intravenous
• Intramuscular
• Subcutaneous
• Intra-arterial
• Intrathecal
• Intraosseal
• Intraarticular
• Intraperitoneal

Intravenous Administration

• i.v. administration utilizes aqueous solutions or oil-in-water emulsions (o/w)
• Rapid onset of action
• Irritants can be administered due to vascular walls being relatively insensitive
• Long-term cannula use carries a risk of infection (max 4 days)
• Suspensions and emulsions with droplet sizes above 0.5 μm are not suitable for IV administration
• Drugs that precipitate blood components or hemolyze erythrocytes should not be administered intravenously
• Substances that scavenge physiological ions, like tetracycline, are not suitable for IV administration

Intramuscular Administration

• i.m. administration involves solutions, suspensions, or emulsions in an aqueous or oil vehicle
• It is appropriate when a quick effect is needed, but IV administration is dangerous, such as in anaphylactic shock
• It's used if IV application is impossible (aggressive patient, epileptic seizure)
• Slower onset of action compared to IV
• Only non-irritating drugs should be administered intramuscularly
• Can cause pain in some drugs
• There is a possibility of local complications such as inflammation, necrosis, and infection

Subcutaneous Administration

• s.c. administration means low level resorption is constant and slow
• Resorption can be modified by adjusting the solubility of LL, or the addition of a vasoconstrictor/vasodilator, or a proteolytic additive to enlarge the surface of the subcutaneous tissue
• Application is simple, even for a layman
• Absorption is slower than i.v. and i.m.
• Irritating drugs should not be administered via this route
• Soreness if possible when applying certain drugs
• There is possibility of local complications, including inflammation, necrosis, and infection

Other Methods of Applying Parenterals

• Intra-arterial administration has limited use, achieving a specific effect in a particular tissue or organ
• Intrathecal administration provides a rapid effect at the level of brain cells and the cerebrospinal axis
• Intraosseous administration is used to deliver drugs to the bone, exceptionally
• Intraarticular administration involves injecting drugs into the joint slit in the case of joint diseases
• Intraperitoneal administration involves injecting drugs into the abdominal cavity through the peritoneum, with absorption comparable to IV application, as with antibiotics in severe peritonitis

Injection (Iniectiones)

• Sterile solutions, emulsions, or suspensions with an antimicrobial additive
• Volume limited to a maximum of 100 ml
• Administered via a single needle injection
• i.v. injections should ONLY consist of aqueous solutions
• Especially beneficial for drugs with a high first pass effect
• Used in urgent situations or with uncooperative patients, such as in unconsciousness
• Depot forms involve choosing the application location or influencing the solubility of the active substance
  • Properties of the molecule are adjusted by selections of solvents, and injections with an oil vehicle being absorbed more slowly

Infusion (Infusiones)

• Sterile, non-pyrogenic aqueous solutions or oil-in-water (o/w) emulsions with water as an external continuous phase
• Volume ranging from 100 to 1000 ml
• Usually isotonic and contain very few stabilizing additive
• Intended for gradual cannulation by drip into a vein at a rate of 100-500 ml/h, typically into the v. cephalica antebrachii or v. jugularis interna
• Infusion sets consist of the connection between the cannula and the infusion bottle

Purpose of Infusions

• Modification of water and electrolyte homeostasis disorders
• Adjustment of acid-base balance
• Parenteral nutrition
• Temporary replacement of blood or plasma
• Osmotic diuresis
• As carrier solutions for pharmaceuticals to maintain stable plasma concentrations
• Infusion of ions (saline Hartmann‘s s., Darrow‘s s., Ringer‘s s.,...), carbohydrates, amino acids, fats

Parenteral DF with Controlled Release

• For i.m. application, all or part of a depot injection with microparticles remains at the injection site
• The depot gradually releases the drug into the tissue fluid for subsequent absorption
• Rate of release of active substance (AS) is affected by the composition of the injection:
  • Aqueous solution: fastest absorption rate into the systemic circulation
  • Aqueous suspension
  • Oil solution
  • Aqueous emulsion o/w
  • Oil emulsion w/o
  • Oil suspension: slowest absorption rate

Implants (IMPLANTATA) for Systemic Use

• Single-dose sterile solid rod formations, sometimes strongly viscous fluids with the drug
• Placed in the tissue by a special injector or surgical intervention
• Used to achieve prolonged AS intake for systemic therapy

Micronized Injections

• Liposomes: vesicles with lamellar structure, formed from the dispersion of phospholipids in an aqueous medium
  • The core and surface are hydrophilic, and hydrophobic drugs become located on the inside of the membrane (lipophilic location)
  • Passive and active targeting
• Niosomes, pharmacosomes

Implants (IMPLANTATA) for Targeted Action

• Creating a high concentration of AS in the immediate proximity of the treatment site
• Supplying cytostatics to inaccessible places such as the central nervous system (CNS) or bone tissue
• Coronary stents coated with immunosuppressants and intrauterine devices

DF for Topical Administration on the Skin and Its Adnexa

• Dermatologica

DF for Skin Use - Dermatologica

• Treatment of skin diseases and preventive skin protection
• Liquida cutanea:
  • Solutions, suspensions, emulsions, shampoos, foams
• Praeparata semisolida ad usum cutaneum:
  • Ointments, creams, gels, and pastes
  • Skin patches with pharmaceuticals
• Pulveres adspersorii:
  • Powders

General Rules for Application of Dermatological Preparations

• The choice of preparation and vehicle corresponds to the intensity and stage of the disease
  • Wet: “Wet” preparations like hydrophilic solutions, lotions, gels, and creams
  • Dry: “Dry” preparations like anhydrous hydrophobic ointments
• Acute diseases of stronger intensity use hydrocreams and hydrogels
• Chronic diseases of weaker intensity use hydrophobic ointments and oleocreams

Groups of Dermatological Preparations by Effect

• Disinfectants and antiseptics: cleanse the skin, damage, or destroy germs
• Antiseborrheics: reduce excessive sebum production
• Astringents: dry out and tighten minor injuries
• Antipruriginosis and local anesthetics: prevent itching and local desensitization
• Antihidrotics: fight excessive sweating, clogging, or dampening sweat glands
• Keratoplastics and keratolytics: affect the stratum corneum of the skin
• Antipsoriatics: palliative action in psoriasis
• Steroid and other anti-inflammatory drugs: inhibiting the formation of mediators of inflammation

Liquid Skin Preparations - Liquida Cutanea

• Solutions:
  • Aqueous, alcoholic, and oily solutions
  • Application through compresses, brush, and tampon
    • Aluminum acetate solutions are astringent swelling compresses and mouth rinses
    • Gentian violet solutions are used as a methylrosanilinii chloride
• Suspension
  • Suitable for extensive acute dermatosis, urticaria, eczema
  • Liquid powders comprise talc, zinc oxide, glycerol, ethanol, and water, adding Menthol provides itch relief
  • Granulants and epithelistics (Suspensio Višněvski)

Liquida Cutanea

• Shampoos:
  • Emulsions, suspensions, or solutions containing surfactants
    • Application to the skin with hair, rinsing with water, and often containing antifungals and other compounds
• Skin Foams:
  • Large volume of gas dispersed in liquid
    • Application to skin or mucous membranes, or other anti-inflammatory foam, or other cooling sensations
• Hydrocolloid dispersion is the cutaneous use of "liquid bandages"
  • Mucous consistency with colloidal particles in a quick drying solvent to protect (broken) skin
    • Collodium for skin solutions warts antiseptics and Viride nitens

Semi-Solid Dermatological Preparations (Praeparata Semisolida Ad Usum Cutaneum)

• Applied to skin or mucous membrane for local, skin penetration, softening and protective effects
• Simple or composite bases
  • Basis dependent upon substance for hydrophilic or lipophilic qualities
• Added Ingredients: Antimicrobial, anti-oxidants emulsifiers, stabilizers, penetration enhancers etc
• Sterile: Required for open wounds and damaged skin

Praeparata Semisolida Ad Usum Cutaneum

• Ointments (Unguenta)
• Creams (Cremores)
• Gels (Gelata)
• Pastes ad usum dermicum (Pastae ad usum dermicum)
• Patches with drugs (Emplastra medicata)

Ointments - Unguenta

• Base is single-phase and mixed with solid/liquid substances
• There are separate ointment foundations, however, these do not contain drugs
  • Hydrophobic, lipophilic and resist water, but wash poorly, typically with animal fats, waxes or paraffin
  • Hydrophilic, lipophobic and water-miscible

Ointment Foundations (Bases)

• Vaselinum album (white Vaseline)
• Vaselinum flavum (yellow Vaseline)
• Adeps suillus (pork lard)
• Adeps lanae (fat from sheep's wool)
• Unguentum simplex (simple ointment)
• Synderman
• Macrogoli unguentum

The Use of Ointments

• Use is according to the active substance
  • Anti-inflammatory (corticosteroids - dexamethasone, mometasone...)
  • Keratolytics (Acidi salicylici unguentum 10-20%)
  • Keratoplasty and antiseborrheics (Acidi salicylici unguentum 0.5-3%)
  • Disinfectants and antiseptics
  • Protective and lubricating
  • Antibiotics and antifungals
  • Granulants and epithelistics
  • Antipruriginosis and antipsoriatics

Creams - Cremores

• Semi-solid with aqueous and oily components
• Composed of 10% water at a minimum
• Can also have a base consisting of just emollients
• Bases come from Ambiderman and Ambiderman
• Action is attributed Astringent, Protective, disinfectant, Virostatic agents.

Gels - Gelata

• Contains a gel-forming substance (polymers, surfactants) and environment (usually water)
• Includes a gelation and three-dimensional mesh shape.
• Examples of gel-forming substances: Carbomera Tritici amylum, Gelatina, Silica colloidalis anhydrica etc.
• Has cooling affects - can be pruritic and anti-inflammatory

Paste -- Paste

• Made of ointment, creams, bases and a high compound of 25-50 solids
• The water level should stay above 10%.
• Contains also astringents and antifungals
• May give yellow if it is 3% tetracycline

Powders - Pulvers adspersorii

• Particles are vary degrees, however they must be lose dry
• All particles will have their own absorbent properties and will have astringent to anti-imflammatory properties
• Covering is another feature to these properties of the powdery surface, that decreases friction

Medicinal Patches - Emplastra Medicata

• Patches that intend to apply AS evenly on carriers through a thin flexible application
• Patches keep AS in contact with area for AS to absorb - or will have keratolytic effects
• Carrier must be cut to be applied
• A common material is 40% salicyclic alcohol to be applied as an adhesive

Transdermal Therapeutic Systems (TDDS) - Transdermalia

• Applied and put on for transdermal permeation that will penetrate AS through system
  • Applied on dry, clean and un-irritated surfaces and do not apply force (or irritation)
  • Make sure to press skin well
  • To cut, follow SPC procedure
• Often used in HRT treatments, or smoking cessation or cancer treatment

Transdermalia - Advantages and Disadvantages

• Easy application, Bypassing the first, Plasma concentration
• Potential Adhesion issues, and skin irritation

Ocular DF

• Includes Ophthalmology of the eyes

Ocularia

• Created to be for treatment around the eye from the frontal of the inner eye and around the Conjunctiva
• Transcorneal Diffusion is critical but roughly only over 1% will be retained

Ocularia

• Eyedrops, oculoguttae and collyria
• Eye waters, Aquae opthalmicae, lotioned
• Made of pulveres to treat - eye waters and other pulveres
• Lastly are Lamellae treatments

Oculoguttae

• Used for short amounts of time, single dose is used
• Volume is roughly 10ml to meet the Pharma guidelines
• Compatible with the eye - no irritation

Rules for Eyedrop Qualities

• Should adhere asepticism / sterility
• Benzalkonii levels .01%/Vehicle injection
• should be easy on the pH to be painless
• Must also have low surface level tension - viscosity

Applying Eyedrops

• Apply one drop in the eye, and push in

Eye Waters for - Aquae Opthalmicae

• Can be aqueous water made for washing for eye or limited short use
• can act upon osmolality, PH and other qualities
• Can serve as anti-imflamatory

Eye Injections

• Intention of applications is for the conjunctive area or anterior bodies 1ml is max - often antibiotic and corticosteroid

Semi-Solid and Rigid Eyedrops

• Includes ointments and cream Can used with a cap for sterilized purposes
• Does not irritate membranes
• Uses Ophthalmic Symplex in Ointments.
• For insertion of eye matrix to be used in insertion points

Nasal and Ear DF

• Nasalia Et Auricularia

Nasalia

• Made for the nasal cavities - membrane affects the ciliary walls
• often serve as anti-histamines
• Systemic qualities are a very poor for there fast pass

Nasalia

• All liquids and liquid sprays must pass through aero-dispersement Nasal Wash To be inserted into skin Includes lotions as often ointments in topical format Lastly one might treat it

Nasalia

• Properties will cause the PH levels of the isotoronic liquid make the mucus very adhesive and for its surface

Nasalia

• Should maintain a moisture balance Cilia needs to move and it effects temp and flow. Applied and spraying properly.

Auricularia

• Used exclusively through the canal. Or for ear lavage
• With drops, washer and tampon for all different problems, sterilized is key.
• Its should maintained body temperature
• Key compound used for antiseptics as well

Rectal and Vagina DF

• Rectilia Et Vaginalia

Rectilia

• Treated for both local and systematic reasons
• Good for vomiting patients
• Bypasses the pass by 50
• Good for fast

Suppositoria

• Often used for rectum Can maintain -2-3ml, Includes base compounds like Olleum cacao.

Suppositores

• Used for patient to be uncooperative, (young /old) Local level treat hemorrhoids

Reital df

Liquid reital DF

• can used with liquid - but with a applicator

Semisolid

Can often treat hems

Vaganalis

• Can be solid, liquid or semisolid for local and systematic insertion Liquid vaginal can be useful

Used for water based components like ph - used often for infections Vagianls serve for

Globing vaganis

• Can insert sperical balls in vagina To treat for hormones Used in microflora / anti fungal infections

DF FOR INHALANDALATION

INHILAINA

INALIINDA

Treating for aerosols for both

• Both small and local

INALATION SYSTEMS

ACTIVE AND PSASIE

Medicnal

Pure has system designed for therapy

Botttel must be sterilized

• Must be instructed on what its used for .