Pharmaceutical Dosage Forms

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

2. 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. 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. 4 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. 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. 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. 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. 8 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.

9. 9 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

10. 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. 11  - 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.

12. 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. 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. 14 Classification of pharmaceutical dosage forms according to physical properties Gaseous dosage forms Liquid dosage forms Semisolid dosage forms Solid dosage forms

15. 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. 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. 17 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

18. 18 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 (> 25%, e.g. ZnO) are dispersed in ointments � mostly oleaginous (Petrolatum)

19. 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. 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. 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. 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. 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. 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. 25 Parts of prescriptions

26. 26 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.

27. 27 Parts of prescriptions

28. 28 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")

29. 29 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."

30. 30 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.

31. 31 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"

32. 32 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.

33. 33 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.

34. 34 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.

35. 35 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.

36. 36 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.

37. 37 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.

38. 38 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.

39. 39 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.

40. 40 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.

41. 41 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.