Pharmaceutical Technology II Nahed Hegazy, PhD

Table 1

A dosage form can be designed to overcome suboptimal physicochemical or

biological properties of a drug or route of administration.

Design of dosage form to overcome drug travel challenges

Factor Dosage form design Example
Poor water solubility Use of surfactants in tablets Lipitor, Septra DS
Use of cosolvents to make a Lorazepam, diazepam,
solution dosage form phenytoin, phenobarbital
Preparation of a soft gelatin Lanoxin, Prometrium
capsule
Preparation of liposomal Amphotericin liposomal
formulation preparations
Poor permeability Use of pH modifiers to Lidocaine patch
increaseconcentration of
unionized form
Use of absorption promoters Butrans
Carrier made from drug and Transceptor drug delivery
part ofan immunoglobulin technology
capable ofentering epithelial
cells via receptormediated
cytosis
Retention of the drug at Slow eroding ocular inserts OcusertR for sustained
the site of absorption delivery of ophthalmic drugs
Mucoadhesive dosage forms Striantmucoadhesive buccal
that stick at the absorbing tablets
membrane
Drug instability at Preparation of enteric coated Omeprazole and other
extreme pHs dosage forms proton pump inhibitors
Rapid drug metabolism Preparation of extended Morphine sulfate extended
release tablets and capsules release tablets can be
administered once or
twice daily rather than six
times daily
Linking polyethylene glycol Pegfilgrastim (Neulasta)
to protein molecules to solution for injection,
reduce their elimination by pegaptanib (Macugen)
amidases and the solution for injection,
mononuclear phagocytic pegaspargase
system (Oncaspar) solution for
injection

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 Pharmaceutical Technology II Nahed Hegazy, PhD

Extensive drug Preparation of sublingual Nitroglycerin tablets

metabolism dosage forms
Formulation with enzyme Levodopa/carbidopa
inhibitors
Selective site delivery Respiratory drugs are Proventil HFA, Ventolin HFA,
delivered by aerosol AdvairDiskus
inhalation
Enteric coats for delivery to Pentasa, Asacol
colon
Targeted delivery systems Herceptin, Rituxan, Erbitux
Controlled rate of Infusion pumps Insulin pumps
delivery Reservoir transdermal TransdermScop, Transderm
patches Nitro, Estraderm, Androderm
Osmotic oral dosage forms OROS, GITS and COER
technology
Table 2
Issues relating to patient use of dosage forms
Dosage form Issue
Tablet or capsule Takes without water resulting in sticking to the esophagus and
subsequent mucosal injury
Extended release Use as an as needed medication not helpful because of slow
tablet or capsule release properties
Crushing results in conversion to an immediate release form
Enteric coated tablets Crushing exposes the drug to stomach acid or the stomach lining
to the drug
Buccal or sublingual Swallowing results in extensive loss of the drug to first pass
tablets metabolism
Suspensions Failure to shake well results in non-uniform doses
Eye drops Failure to wait 5 minutes between drops to the same eye results in
loss of the second dose
Nose drops Head back administration results in loss of drug to the
nasopharynx
Suppositories Must be unwrapped
Metered dose inhalers Fails to empty lungs; mis-times activation of device with
inhalation; fails to hold breath resulting in less medication reaching
the lungs
Fails to rinse mouth after inhaled corticosteroids resulting in oral
thrush infections
Dry powder inhaler Swallows capsule rather than inhaling with dry powder inhaler
capsules
Transdermal patches Placement must be rotated
Reservoir devices should not be cut

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 Pharmaceutical Technology II Nahed Hegazy, PhD

Table 3

Effect of disease processes on drug travel from dosage form to

receptor
Disease state Effect
Absorption
Dysphagia (myasthenia gravis, elderly) Difficulty delivering drug to site of absorption
Achalasia (inability to empty esophagus) Difficulty delivering drug to site of absorption
Asthma/emphysema increased airway Difficulty delivering inhaled drug to site of
resistance absorption
Achlorhydria; pH of gastric fluids ≥6.5 Reduced absorption of atazanavir,
ketoconazole, digoxin, calcium, vitamin B12,
iron, vitamin C
Liver disease Slow gastric emptying; slow oral drug
absorption
Vomiting Loss of medication from the route of
administration
Distribution
Obesity changes the lean to fat tissue ratio Dosing metric will depend on drug
lipophilicity – use total body weight for
lipophilic drugs and lean body mass for
hydrophilic drugs
Circulatory shock reduces cardiac output Reduces drug distribution to peripheral
tissues
Multiple sclerosis, AIDS/AIDS related Increased permeability of blood–brain
dementia, Alzheimer's disease, barrier
encephalitis/meningitis, Hypertension,
seizure disorder

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 Pharmaceutical Technology II Nahed Hegazy, PhD

Liver disease, reduced protein synthesis
Inflammatory diseases, stress, malignancy
Chronic kidney disease, loss of protein
through kidney
Metabolism
Liver disease reduced phase I enzyme
activity, phase II enzymes less affected
Elimination
Acute renal failure
Chronic renal failure progressive loss of
functioning nephrons
Biliary obstruction
Decreased albumin; more unbound drug
Increased alpha-1 glycoprotein; more bound
drug
Decreased albumin; more unbound drug
Decreased metabolism of morphine,
nifedipine, lovastatin, metoprolol, and others
Sudden, reversible reduction in renal
elimination of drugs
Reduction in renal elimination of drugs:
amikacin, cephalexin, digoxin, gentamycin,
hydrochlorothiazide, and others
Reduces drug and metabolite elimination in
the feces

Table 4

Predicted effects of genetic variations in metabolic enzymes

Metabolizer Effect on drug Effect on Effect on Effect on
phenotype patient prodrug patient
Ultrarapid (UM) Rapid Reduced Rapid activation Increased
deactivation of Therapeutic of the drug therapeutic or
the drug effect adverse effect
Extensive (EM) Extensive Expected Extensive Expected
deactivation of therapeutic activation of the therapeutic or
drug, considered effect drug adverse effect
the normal
phenotype
Intermediate Lower than Increased Lower activation Reduced
(IM) normal therapeutic or of the drug therapeutic or
deactivation of adverse effect adverse effect
the drug
Poor (PM) Loss of drug Increased Loss of drug Reduced
deactivation via therapeutic or activation via therapeutic or
this enzyme adverse effect this enzyme adverse effect

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