1. Pharmaceutical Dosage Forms
Presented By
Prof. Dr. Sanaa A. El-Gizawy

2. 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.

3. 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)

4. Accurate drug dosing can be difficult or impossible
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

5. 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

6. 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

7. 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

8. 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.

9. 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

10. 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

11. 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 % range as compared with the original preparation.

12. 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.

13. 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)

14. Classification of pharmaceutical dosage forms according to physical properties
Gaseous dosage forms
Liquid dosage forms
Semisolid dosage forms
Solid dosage forms

15. 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)

16. 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

17. Semisolid dosage forms 1- 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

18. Semisolid dosage forms 1- 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 (> 25%, e.g. ZnO) are dispersed in ointments – mostly oleaginous (Petrolatum)

19. 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.

20. 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)

21. 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

22. 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)

23. 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.

24. 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.

25. Definition and Format
A prescription is a written, verbal, or electronic order from a practitioner or designated agent to a pharmacist for a particular medication for a specific patient.

26. Writing Prescriptions Who can write a Rx?
Practitioners
Physicians, veterinarians, dentists, podiatrists
Mid-level practitioners
nurse practitioners, physician assistants, optometrists, pharmacists

27. Definition and Format Sample of Generic Hospital Prescription
Sample of Physician Specific Prescription

28. Contents of the Prescription
Under Texas State Law, all prescriptions should have the following essential elements:
Date of the order
Patient Name and Address
If the drug is prescribed for an animal, the species of the animal
Name of the drug
Strength of the drug
Quantity of the drug
Directions for use
Intended use of the drug, unless practitioner feels indication is not in best interest of patient
Practitioner Name, Address, Telephone number

29. Parts of prescriptions

30. For Arthur H. Recipe
Take thou
Potassium Acetate of one 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.

31. Parts of prescriptions

32. 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")

33. 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."

34. 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.

35. 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"

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.