Pharmaceutics and Drug Delivery

• Pharmacists consider drug delivery, its effect on the medical condition, and therapy efficacy.

Pharmaceutics

• Pharmaceutics focuses on the relationship between drug formulation, delivery, disposition, and clinical response.
• Pharmaceutics involves designing, engineering, and preparing dosage forms, as well as preparing, using, or dispensing medicines.

Dosage Form Considerations

• Severity of the indication, route of administration, safety, effectiveness, cost, and patient compliance all factor into selecting a dosage form.

Route of Administration Impact

• Systemic or local action is a key consideration for route of administration.
• IV provides immediate systemic distribution.
• SC and IM routes require absorption time into the blood
• Oral administration generally results in the slowest absorption.
• Sublingual administration allows rapid absorption via the oral mucosa, with the potential for re-processing of unabsorbed medication.

Administration Examples

• Haloperidol tmax: IM reaches peak plasma concentration in 20 minutes; PO takes 2-6 hours.
• Sumatriptan's initial response: SC route takes 10-60 minutes; PO route takes 1-2.5 hours.
• Insulin's onset: SC takes 30-90 minutes; IV is immediate.

Systemic vs. Local Action

• IV, SC, IM, and oral routes are systemic.
• Transdermal is systemic.
• Topical applications like ointments and creams are local.

Mixed Action

• Inhalable drugs (oral or nasal) have both local and potential systemic effects.
• Albuterol is used for bronchodilation, but some absorption could lead to tachycardia.

Safety Considerations

• An Adverse Drug Event (ADE) is any injury, large or small, caused by the use of a drug.
• Non-preventable ADEs occur despite common and accepted drug use.
• Preventable ADEs result from errors in the medication use system, such as prescribing, dispensing, administering, or monitoring.
• Prescribing errors are the most common source of medication errors.
• Selecting an inappropriate dosage form is also a common prescribing error.

Effectiveness

• Different formulations of the same active ingredient can vary in effectiveness.
• Diltiazem CR is better at suppressing morning anginal attacks versus Diltiazem.
• Nifedipine CR was found to be an effective antihypertensive.

Healthcare Costs

• Out-patient insurance plans have reimbursement tiers (generic, preferred brand, non-preferred brand); low cost and compliance are important.
• In-patient insurance companies reimburse a set amount for diagnoses; hospitals prioritize low costs.

Compliance Factors

• 20-30% of prescriptions are never filled, and 50% are not taken as prescribed.
• Non-compliance leads to $100-300 billion in avoidable healthcare costs, 125,000 annual deaths, and 10% of hospitalizations.
• Factors affecting compliance include pill burden, dosing frequency, patient preference, mental/physical disabilities, and cost.
• Simplification of dosing from 3x to 1x per day improved compliance from 59% to 84%.

Drug Delivery

• A "drug product," not just a "drug," is administered, with the drug product being the drug and a dosage form.
• Dosage Form: a system designed to deliver a precise quantity of medicinal agent to a specific body location, maximizing therapeutic effects and limiting side effects.

Dosage Form Features

• A quality dosage form will deliver the proper amount at the appropriate rate and provide reproducible doses
• A quality dosage form will also maintain the drug's chemical stability and avoid incompatibilities.
• A quality dosage form will possess pleasing pharmaceutical qualities and be suitable for large-scale manufacturing.

Dosage Form Types

• Dosage forms classified by physical state (solids, liquids, etc.), application point/delivery route (oral, nasal, etc.), delivery mode (systemic or local), and technology of release (conventional or modified).
• Oral dosage forms deposit the drug in the gastrointestinal tract and release the dose for absorption into the bloodstream.
• Oral dosage forms utilize Gl absorption functionality.

Oral Dosage Forms

• Oral Solid: Tablets, capsules, and powders are common solid oral dosage forms.
• Oral Liquid: Solutions and dispersions are liquid oral dosage forms.

Solid Oral Dosage Forms Need:

• Solid oral dosage forms development needing a consideration of: physical, chemical, mechanical, and biopharmaceutical properties for stable, bioavailable, and deliverable product.

Drug Properties

• Aqueous Solubility: Drug concentration in equilibrium with the solid phase, affects bioavailability, depends on temperature/pressure.
• Formulation strategies increasing amount available in solution when not soluble such as using less stable amorphous form can help.
• Dissolution Rate: How quickly a drug enters solution (kinetic property); solubility is equilibrium (thermodynamic property).
• Fast-dissolving tablets address dissolution, and particle size impacts the dissolution rate.

Crystalline State

• Crystalline State: Drugs possesses long-range order, unit cells repeating in three dimensions, sharp melting points, same molecular conformation.
• Crystal Lattice: Other molecules (solvates, hydrates, co-crystals) or salts (anions/cations).

Polymorphism

• Polymorphism: Ability of a substance existing in two+ crystalline phases; differ in arrangement/conformation in crystal lattice.
• Slight changes modify stability, bioavailability, processing.
• Crystal State: Polymorphs having the same empirical formula and is seen in 1/3 of organic substances.
• Excipients/processing and each polymorph is patentable.

Amorphous Solids

• Amorphous Solids: Drugs that lack long-range order but higher solubility than crystalline forms, better bioavailability for poorly soluble drugs, are unstable/crystallize
• Polymers use are added to stabilize the amorphous solids.

Oral Solid Dosage Forms

• Common oral solid dosage forms include tablets, capsules, loose and lyophilized powders, and controlled-release matrices.

Tablets

• Tablets: Solid dosage units contain compressed ingredients, in a variety of shapes/sizes, provide ease in handling/swallowing, can be dosed in different APIs
• Dosage adjustments can also be accomplished by breaking, can be coated for taste/odor concerns, and easy to manufacture
• Tablets can be difficult to adulterate, contain active and inactive ingredients, and are expressed as a % of weight based.

Tablet Ingredients

• Excipients used: aids processing, ensures stability/bioavailability, assist id, overall effectiveness of product storage.
• Physicochemical Identifiers (PCID): Authenticating product for flavors, pigments, inks.

Oral Tablet examples

• Oral Tablets include:
  • Conventional
  • Chewable (Pepsid, Isordil, Children's OTC)
  • Modified release (Glucotrol XL) such as Enteric coating to release in the intestine
  • Sublingual, buccal, dissolving tablets - Nitroglycerin under tongue, buccal between gum.

Tablets Not Intended to Be Swallowed

• Effervescent tables use water like alka seltzer
• Vaginal tablet like Mycostatin use a specific route

Other Tablets

• Chewable Tablets: Soft tablets need flavoring for patient.
• Enteric-Coated Tablets: Coatings protect from stomach acid by using:
  • Insoluble coat at low pH that prevents disintegration and dissolution
  • Soluble coat at higher pH protects from storage and drug in stomach

Sublingual and Buccal Tablets

• Administer these between the tongue.
• Small tablets design to rapidly release in the oral cavity.
• Effervescent Tablets: Contains acids to produce C02, mask easy, increase solubility.

Tablet Excipients

• Tablet Ingredients: Excipients source is listed in source handbook, the materials must be inert to the body and safe.

Tablet Ingredients: types

• Diluents add weight practical weight.
• Microcrystalline is use to keep table held is use to have good manufacturing.
• Disintegrates are different types to break up in a sold in water like sodium chloride,.

Tablet Ingredients: Binders

• Binders add machine strengthen to dissolving or swelling.
• Prevents lubricant stick can reduce flow with different types.
• Stearate reduce surface tension increase to be less fluffy.

Tablet Ingredients: Controlled Release

• Control releases with layers, and polymer by using xanthan or Eudragits.
• Improves color, id, and also used as sugars if approved.

Tablets: Dosage and Release

• D,L curves must a blood level over long period need to long to effect.
• Need slow release in tablet, to allow absorbtion in solution in body with water.

Capsule Components

• Requires a lot of water with a solid form gel to be hard to open to contain liquid.
• May contain collagen for test, not always need for flavor.