Pharmaceutical Dosage Forms

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Pharmaceutical Dosage Forms

• Presented
• By
• Prof. Dr. Sanaa A. El-Gizawy

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Pharmaceutics

• Pharmaceutics is the science of dosage form
  design.
• There are many chemicals with known
  pharmacological properties but a raw chemical is
  of no use to a patient.
• Pharmaceutics deals with the formulation of a
  pure drug substance into a dosage form.

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Active Drug Substance

• (Active pharmaceutical ingredient - API)
• Chemical compound with pharmacological (or other
  direct effect ) intended for use in diagnosis,
  treatment or prophylaxis of diseases.
• International non-proprietary names (INN, generic
  names)

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Direct clinical use of the active drug substances
as they are is rare due to a number of good
reasons

• API handling can be difficult or impossible
  (e.g., low mg and ?g doses)
• Accurate drug dosing can be difficult or
  impossible
• API administration can be impractical, unfeasible
  or not according to the therapeutic aims
• Some API can benefit from reducing the exposure
  to the environmental factors (light, moisture),
  or they need to be chemically stabilised due to
  the inherent chemical instability

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Direct clinical use of the active drug substances
as they are is rare due to a number of good
reasons

• API can be degraded at the site of administration
  (e.g., low pH in stomach)
• API may cause local irritations or injury when
  they are present at high concentrations at the
  site of administration
• API can have unpleasant organoleptic qualities
  (taste, smell compliance!)
• Administration of active substance would mean to
  have no chance for modification (improvement) of
  its PK profile

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From drug substance to pharmaceutical preparation

• Besides the choice of the active drug substance,
  you need to also make a responsible decision
  regarding the route of administration and the
  DOSAGE FORM (drug delivery system) wrong choice
  can cause failure of therapy
• You should also be able to handle and administer
  the drug properly or advise the patient about it
  wrong use can cause failure of therapy

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Excipients

• Excipients (inactive pharmaceutical ingredients)
• Its selection depends on technological,
  biopharmaceutical and/or stability reasons.
• Diluents/fillers, binders, lubricants, coatings,
  preservatives, colorants and flavouring agents

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Pharmaceutical dosage form

• Pharmaceutical dosage form
• Determines the physical form of the final
  pharmaceutical preparation
• Is a drug delivery system which is formed by
  technological processing (drug formulation)
• Must reflect therapeutic intentions, route of
  administrations, dosing etc.

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Pharmaceutical preparation (PP)

• Pharmaceutical preparation (PP)
• particular pharmaceutical product containing
  active and inactive pharmaceutical ingredients
  formulated into the particular dosage form.
• Packed and labelled appropriately
• Two major types of PP according the origin
• Manufactured in large scales by pharmaceutical
  industry (original and generic preparations)
• Compounded individually in compounding pharmacies

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1- Pharmaceutical preparations manufactured by
pharmaceutical industry

• 1.1- Original pharmaceutical preparations
• undergo full and very extensive pharmacological/
  toxicological and pharmaceutical pre-clinical and
  clinical development and evaluation
• particularly important is the proof of
  effectiveness and safety

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1.2- Generic pharmaceutical preparations
(authorised copies of original preparations)

• - Can be released after the expiration of the
  patent protection of the original preparation
• The approval for clinical use is easier due to
  the prior experience with the original
  preparation
• Must be pharmaceutically equivalent same API,
  dose, pharmaceutical dosage form and the same
  route of administration as in original
  preparation
• Must be clinically bioequivalent i.e. it must be
  of very close PK profile as original preparation.
  PK parameters (Cmax, tmax, AUC) are within 80-125
  range as compared with the original
  preparation.

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2- Pharmaceutical preparations compounded
individually

• These PP are compounded individually for a
  particular patient according to the physician's
  prescription in a pharmacy licensed for
  compounding
• In contrast to the past, they are used rather
  rarely and mostly in specific situations
• It is highly advisable that whenever the
  particular suitable PP is approved and
  commercially available it should be preferred
  over the compounding
• The major disadvantage is the lack of
  standardization (it is always a single-patient
  batch), unavailability of rigorous QC testing
  and the appropriate clinical evaluation.

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The individually compounded PP can be a justified
choice when

• The drug in a particular dosage form is not
  commercially available on the market
• The extraordinary low or high dose is needed
  (young children, elderly people, special
  situations e.g., intoxications). In this case
  right dosage strength need not be readily
  commercially available for every patient
• The patient suffers from the allergy on a
  specific excipients (e.g., lactose a filler,
  some colorizing/flavouring or antimicrobial
  agents - parabens) or another drug appearing in
  the PP
• Patient is unable to use a PP in its commercially
  available dosage form (e.g., children, elderly)

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Classification of pharmaceutical dosage forms
according to physical properties

• Gaseous dosage forms
• Liquid dosage forms
• Semisolid dosage forms
• Solid dosage forms

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Gases

• Medicinal gases, inhalation/volatile anaesthetics
  (vaporised before administration by inhalation)
• Aerodispersions of solid particles (e.g.,
  antiasthmatic inhalations) or liquid particles
  (antiasthmatic inhalations or sprays)

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Liquids

• Solutions one homogenous phase, prepared by
  dissolving one or more solutes in a solvent
• Emulsions
• a dispersion system consisting of two immiscible
  liquids
• o/w or w/o
• cloudy appearance
• Suspensions
• A dispersion system where solid particles
  (dispersed phase) are dispersed in liquid phase
  (dispersion medium)
• According to the size of dispersed particles (1
  nm- 0,5 mm) a molecular, colloidal and coarse
  dispersions can be distinguished
• May require shaking before administration
• Not intended for systemic administration of drugs
  with high potency

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Semisolid dosage forms1- Unshaped (without
specific physical shape)

• Gels -A semisolid systems in which a liquid phase
  is constrained within a 3D cross-linked matrix.
• Creams semisolid emulsion systems (o/w, w/o)
  containing more than 10 of water.
• o/w creams - more comfortable and cosmetically
  acceptable as they are less greasy and more
  easily water washable
• w/o creams accommodate and release better
  lipophilic API, moisturizing, Cold creams

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Semisolid dosage forms1- Unshaped (without
specific physical shape)

• Ointments semisolid dosage forms with the
  oleaginous (hydrocarbon), water-soluble or
  emulsifying base
• Oleaginous (hydrocabon) base Petrolatum
  (Vaseline white, yellow)
• Water-soluble base Polyethylenglycol (PEG)-
  ointment syn. macrogol ointments
• Pastes semisolid dispersion system, where a
  solid particles (gt 25, e.g. ZnO) are dispersed
  in ointments mostly oleaginous (Petrolatum)

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Semisolid dosage forms

• 2- Shaped
• Suppositories (for rectal administration)
• different shapes
• Melting/dissolving at body temperature
• Oleaginous (cacao butter, adeps neutralis) or
  aqueous (PEGs, glycerinated gelatine)
• Pessaries (vaginal suppositories)
• Similar as above, PEGs or glycerinated gelatine
  are often used as base.

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Solid Dosage Forms

• Unshaped (without specific shape)
• - powders for external/internal use
• Shaped
• Tablets
• Capsules
• Implantates (Sterile disks inserted surgically
  into body tissues and designed to release drug(s)
  over extended period of time)
• Transdermal patches
• Lozenges (consists of sugar and gum to medicate
  the mouth and throate)

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Classification of pharmaceutical dosage forms
according to the route of administration

• for systemic administration
• Peroral (p.o)
• Sublingual (S.L) and buccal.
• Rectal
• Parenteral
• Transdermal
• Inhalation

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Classification of pharmaceutical dosage forms
according to the route of administration

• for local administration
• Topical (on the skin or mucosa)
• Into/onto - the eye, nose, ear
• - the oral cavity
• - the vagina, rectum
• - the brochi
• - the skin
• Local parenteral (viz Parenteral above)
• Oral (local effect within GIT antacids,
  adsorbents)

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Prescription Writing

• The prescription is one of the most important
  therapeutic transactions between physician and
  patient.
• The art of prescription writing is an ancient
  inheritance.
• The ancients started their prescription with an
  appeal to the gods for its success.
• The ancient symbol, Rx, signifying the appeal,
  was established centuries ago and has been
  carried down to the present time.

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Prescription Writing

• To avoid undesirable and/or serious effects on
  the patient, both physician and pharmacist must
  render the highest of professional services.
• Accurate diagnosis proper selection of
  medication, dosage form and route of
  administration proper size and timing of dose
  precise dispensing accurate labeling and
  correct packaging all must be provided.

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Parts of prescriptions
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• For Arthur H. Recipe
• Take thou
• Potassium Acetate of.............................o
  ne drachm.
• Of Solution of Acetate of Ammonium........three
  and a half drachms.
• Of Spirits of Nitrous Ether.......................
  ....two drachms.
• Of Infusion of Buchu (a quantity sufficient) up
  to four ounces.........
• Signa -Mix. Let a mixture be made.
• Label -One drachm three times a day after meals.

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Parts of prescriptions
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Form of the Written Prescription

• A prescription consists of the superscription,
  the inscription, the subscription, the signa, and
  the name of the prescriber
• 1- Superscription
• The date when the prescription order is written
  the name, address and age of the patient and the
  symbol Rx (an abbreviation for "recipe," the
  Latin for "take")

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Form of the Written Prescription

• 2- Inscription
• The body of the prescription, containing the name
  and amount or strength of each ingredient.
• 3- Subscription
• The directions to the pharmacist, usually
  consisting of a short sentence such as "make a
  solution," "mix and place into 10 capsules," or
  "dispense 10 tablets."

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Form of the Written Prescription

• 4- Signature
• From the Latin "signa," meaning "write," "make,"
  or "label," this sections contains the directions
  to the patient.
• These should always be written in English
  however, physicians continue to insert Latin
  abbreviations, e.g. "1 cap t.i.d. pc," which the
  pharmacist translates into English, "take one
  capsule three times daily after meals." Since the
  pharmacist always writes the label in English,
  the use of such abbreviations or symbols should
  be discouraged.

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Form of the Written Prescription

• Follow 4- Signature
• The instruction, "take as directed," is not
  satisfactory and should be avoided.
• The directions to the patient should include a
  reminder of the intended purpose of the
  medication by including such phrases as "for
  pain," "for relief of headache," or "to relieve
  itching"

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Form of the Written Prescription

• 5- Labeling
• When the physician wants his patient to know the
  name of the drug, the box on the prescription
  form marked "label" should be checked.
• 6- Refills
• The physician should designate the number of
  refills he wishes the patient to have.

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Proprietary vs. Non-Proprietary ("Generic")
Prescriptions

• In recent years, some hospitals and private
  physicians are indicating on the prescription
  their willingness or desire that the pharmacist
  dispense a non-proprietary or "generic-named"
  preparation instead of the trade name item
  written on the prescription. Some have a box on
  the prescription designated "N.P.P." In this way,
  the pharmacist can use a form of the drug which
  may be less expensive to the patient.

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Types of Drugs

• Legend Drugs These drugs may not be dispensed by
  a pharmacist without a prescription from a
  physician.
• Controlled Drugs In addition to requiring a
  prescription, these drugs require additional
  safeguards for storage. Refills are also limited.
• Over-the-Counter (OTC) Drugs These drugs do not
  require a prescription.

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Controlled Substances

• Schedules of Controlled Drugs These drugs are
  divided into five schedules.
• Drugs can be scheduled, unscheduled, or moved
  from one schedule to another as the need arises.
• Schedule I
• Drugs in this schedule have a high abuse
  potential (narcotic and hallucination effects).
  Examples are heroin, marijuana.

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Controlled Substances

• Schedule II
• Drugs in this schedule have a high abuse
  potential with severe psychic or physical
  dependence liability. Included are certain
  narcotic analgesics, stimulants, and depressant
  drugs. Examples are opium, morphine, codeine,
  hydromorphone, methadone, meperidine, oxycodone,
  anileridine, cocaine, amphetamine,
  methamphetamine, phenmetrazine, methylphenidate,
  amobarbital, pentobarbital, secobarbital,
  methaqualone, and phencyclidine.

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Controlled Substances

• Schedule III
• Drugs in this schedule have an abuse potential
  less than those in Schedules I and II and include
  compounds containing limited quantities of
  certain narcotic analgesic drugs, and other drugs
  such as barbiturates, glutethimide, methyprylon,
  and chlorphentemine. Any suppository dosage form
  containing amobarbital, secobarbital, or
  pentobarbital is in this schedule.

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Controlled Substances

• Schedule IV
• Drugs in this schedule have an abuse potential
  less than those listed in Schedule III and
  include such drugs as barbital, phenobarbital,
  chloral hydrate, ethchlorvynol, meprobabmate,
  chlordizepoxide, diazepam, oxazepam,
  chloroazepate, flurazepam, etc.

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Controlled Substances

• Schedule V
• Drugs in this schedule have an abuse potential
  less than those listed in Schedule IV and consist
  primarily of preparations containing limited
  quantities of certain narcotic analgesic drugs
  used for antitussive and antidiarrheal purposes.

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Requirements for Prescriptions Written for
Controlled Substances

• Required Information on the Prescription
• Must be dated and signed on the day it is issued.
  Must have the full name and address of the
  patient.
• Must have the name, address, and registration
  number of the physician.
• May be prepared by the secretary, but must be
  signed by the physician.

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Refilling Prescriptions for Controlled Substances

• Refills for Schedule II drugs are not permitted.
• Refills for Schedule III, IV, and V drugs are
  permitted if the number of refills is indicated
  on the prescription. However, the prescription
  order may be renewed only up to five times within
  six months after the date of issue. After five
  renewals or after six months a new prescription
  order is required.