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CHAPTER V
CHAPTER V
Pharmacokinetics
Absorption
Propranolol HCl is highly lipophilic and almost completely absorbed after oral
administration. However, it undergoes high first-pass metabolism by the liver and on average,
only about 25% of Propranolol HCl reaches the systemic circulation. Peak plasma concentrations
occur about 1 to 4 hr after an oral dose. Administration of protein-rich foods increase the
bioavailability of Propranolol HCl by about 50% with no change in time to peak concentration,
plasma binding, half-life, or the amount of unchanged drug in the urine.
Distribution
Approximately 90% of circulating Propranolol HCl is bound to plasma proteins (albumin
and 1 acid glycoprotein). The binding is enantiomer selective. The S (-) enantiomer is
preferentially bound to 1 glycoprotein and the R (+) enantiomer preferentially bound to
albumin. The volume of distribution of Propranolol HCl is approximately 4litres/kg. Propranolol
HCl crosses the blood-brain barrier and the placenta, and is distributed into breast milk.
Biological half life: 3 6 hr
Metabolism
Propranolol HCl is extensively metabolized with most metabolites appearing in the urine.
Propranolol HCl is metabolized through three primary routes: aromatic hydroxylation (mainly 4hydroxylation), N-dealkylation followed by further side-chain oxidation, and direct
glucouronidation. It has been estimated that the percentage contributions of these routes to total
metabolism are 42%, 41% and 17%, respectively, but with considerable variability between
individuals. The four major metabolites are Propranolol HCl glucuronide, naphthyloxylactic acid
and glucuronic acid, and sulfate conjugates of 4-hydroxy Propranolol HCl.
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Elimination
In healthy subjects, no difference was observed between CYP2D6 extensive metabolizers (EMs)
and poor metabolizers (PMs) with respect to oral clearance or elimination half-life. Partial
clearance of 4-hydroxy Propranolol HCl was significantly higher and of naphthyloxylactic acid
significantly lowers in EMs than PMs.
Therapeutic indication
Hypertension
Propranolol HCl tablets are indicated in the management of hypertension. It may be used
alone or used in combination with other antihypertensive agents, particularly thiazide diuretics.
Angina pectoris due to coronary atherosclerosis
Propranolol HCl tablets are indicated to decrease angina frequency and increase exercise
tolerance in patients with angina pectoris.
Atrial fibrillation
Propranolol HCl tablets are indicated to control ventricular rate in patients with atrial
fibrillation and a rapid ventricular response.
Myocardial infarction
Propranolol HCl tablets are indicated to reduce cardiovascular mortality in patients who
have survived the acute phase of myocardial infarction and are clinically stable.
Migraine
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Propranolol HCl tablets are indicated for the prophylaxis of common migraine headache.
The efficacy of Propranolol HCl in the treatment of a migraine attack that has started has not
been established, and Propranolol HCl is not indicated for such use.
Therapeutic dosage
Propranolol HCl
Extended/Sustained-Release capsules 60 mg, 80 mg, 120 mg, 160 mg; Inderal LA (WyethAyerst); Betachron E-R (Inwood); Generic; (Rx)
Propranolol HCl for Injection 1 mg/ml in 1 ml amps or vials; Inderal (Wyeth-Ayerst) (Rx),
Generic; (Rx)
Propranolol HCl Oral Solution 4 mg/ml, 8 mg/ml, 80 mg/ml concentrate in 30 ml; Propranolol
HCl Intensol (Roxane); Propranolol HCl (Roxane) (Rx)
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Plantae - Plants
Subkingdom:
Super Division:
Division:
Class:
Magnoliopxida - Dicotyledons
Subclass:
Rosidae
Order:
Fabales
Family:
Genus:
Trigonella L. Fenugreek P
Species:
Group:
Dicot
Description:
Fenugreek, Trigonella foenum-graceum (L), is an erect annual herb native to southern
Europe and Asia. Today, it grows in many parts of the world, including India, southern Africa,
and the United States. The plant reaches a height of 0.3 to 0.8 meters and has trifoliate leaves.
White flowers appear in early summer and develop into long, slender, yellow brown pods.
MAHARAJAHS COLLEGE OF PHARMACYPage 48
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Fenugreek seeds are hard, yellowish brown and angular with a side of about 3mm (1/8
angstroms). These seed may benefit people suffered from various conditions such as wounds,
abscesses, arthritis, bronchitis, and digestive problems. In ancient china herbalists used it for
problems of kidney and male reproductive tracts. People may roast the seeds or store them as
dried seeds.
General Information of Fenugreek
It is an Asiatic herb with aromatic seeds. It is used worldwide as a spice as well as
medicinal herb to soothe the stomach and help to maintain the blood sugar levels. The seeds are
rich in proteins and contain about 50% fiber and 25% soothing mucilage. It is one of the primary
supplements used to support type II diabetes.
Properties: Anticardiarrhal, anti- inflammatory, antiseptic, bitter expectorant.
Nutritional profile:
Fenugreek seeds were calculated on a zero moisture basis per 100g.
Aluminum - 35mg
Cobalt - 0.182mg
Magnesium - 121mg
Ash (Total) - 3.9%
Crude Fiber - 8.7%
Manganese - 0.21mg
Calcium - 73mg
Dietary Fiber - 48%
Niacin - 1.6mg
Calories - 0.68/g
Fat - 6.4%
Phosphorus - 288mg
Carbohydrates - 59.1%
MAHARAJAHS COLLEGE OF PHARMACYPage 49
CHAPTER V
Iron 5.6mg
Potassium 102mg
Chromium 0.04mg
Protein 13.6%
Thiamine 1.25mg
Silicon 0.47mg
Riboflavin 0.32mg
Sodium 58mg
Vitamin A - 38.5 IU
Vitamin C 60mg
Sugars 13%
Starch 15%
Fenugreek benefits
Fenugreek seeds are rich source of trigonelline, lysine and l tryptophan and they also
contain a large amount of steroidal saponins and fibers. These two elements are thought to
account for many benefits of fenugreek. The steroidal saponins may inhibit the cholesterol
absorption and synthesis while fiber is thought to help lower sugar levels. Studies have shown
that fenugreek helped lower cholesterol, blood sugar levels in patients suffered from diabetes.
Fenugreek side effects
Fenugreek appears to be safe at low doses. High doses of fenugreek seeds may cause
gastro- intestinal disturbances and nausea. Fenugreek may stimulate uterine, pregnant women
should avoid fenugreek.
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Sodium starch glycolate is a white to off-white, odourless, tasteless, free flowing powder.
It consists of oval or spherical granules, 30-100m in diameter with some less spherical granules
ranging from 10-35m in diameter.
Solubility: Practically insoluble in water; sparingly soluble in ethanol (95%). In water it swells
up to 300 times its volume.
Stability and storage conditions: It is a stable material. It should be stored in a well closed
container to protect from wide variations in humidity and temperature that may cause cracking.
Incompatibilities: Incompatible with ascorbic acid.
Safety: It is generally regarded as a non-toxic and non-irritant material. However, oral ingestion
of large quantities may be harmful.
Applications: As a disintegrant in tablet (wet granulation and direct compression) and capsule
formulation in 2-8% concentration.
5.4 Crospovidone 89
Structural formula:
Synonyms : Crosslinked povidone, E1202, Kollidon CL, Kollidon CL-M, Polyplasdone XL,
Polyplasdone
XL-10,
Polyvinylpolypyrrolidone
homopolymer.
MAHARAJAHS COLLEGE OF PHARMACYPage 52
(PVPP),
and
1-
vinyl-2-pyrrolidinone
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BP: Colloidal Anhydrous Silica, JP: Light Anhydrous Silicic Acid, PhEUR: Silica, Collidal
Anhydrous, USP-NF: Colloidal Silicon Dioxide.
Empirical Formula: SiO2
Molecular weight: 60.08
Functional Category: Adsorbent, anticaking agent, emulsion stabilizer, glidant suspending
agent, tablet disintegrant, thermal stabilizer, viscosity-increasing agent.
Description: Colloidal silicon dioxide is submicroscopic fumed silica with a particle size of
about 15nm; it is a light, loose, bluish-white-colored, odorless, tasteless, amorphous powder.
Typical Properties:
Melting point: 160C
Refractive index: 1.46
Solubility: practically insoluble in organic solvents, water, and acids, except hydrofluoric acid,
soluble in hot solutions of alkali hydroxide, forms a colloidal dispersion with water.Solubility in
water is 150mg/L at 258C (pH 7)
Specific gravity: 2.2
Stability and Storage Conditions: Collodial silicon dioxide is hygroscopic but adsorbs large
quantities of water without liquefying. When used in aqueous system at a pH 0-7.5. Colloidal
silicon dioxide powder should be stored in a well-closed container.
Incompatibilities: Incompatible with diethylstilbestrol preparations.
Safety: Colloidal silicon dioxide is widely used in oral and topical pharmaceutical products and
is generally regarded as essentially nontoxic and nonirritant excipients.
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Handling Precautions: Eye protection and gloves are recommended. Considering a nuisance
dust, precautions should be taken to avoid inhalation of colloidal silicon dioxide inhalation of
colloidal silicon dioxide dust may cause irritation to the respiratory tract.
Applications:
It is used to promote particulate suspension, eliminate hard settling, and minimize the
clogging of spray nozzles.
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Safety: Described as inert or nuisance dust. Osha has adopted limits of 15mg/m 3 for the total
dust and 5mg/m3 for the respirable fraction. Dust clouds of magnesium stearate may be
explosive. However, oral consumption of large quantities may result in some laxative effect or
mucosal irritation.
Applications: Tablet and capsule lubricant, glidant and antiadherent in the concentration range
of 0.25 to 2.0%.
5.8 Aspartame90
Synonyms: APM, Sanecta, Aspartyl phenylamine methyl ester, Canderel, Nutrasweet, Tri-sweet.
Chemical name: L-aspartic acid, L-phenylalanine
Non proprietary name: USP Aspartame, IP Aspartame, BP Aspartame, Ph.Eur
Aspartamum.
Functional category: Sweetening agent.
Description: It occurs as white and almost odourless crystalline powder.
Solubility: Slightly soluble in ethanol (95%), sparingly soluble in water, solubility increases at
higher temperature and at more acidic pH.
Stability and Storage Conditions: It is stable in dry conditions. In presence of moisture,
hydrolysis occurs. Degradation also occurs during prolonged heat treatment. Bulk material
should be stored in a well-closed container, in a cool, dry place.
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Safety: The WHO has set an acceptable daily intake of 40 mg/kg body weight. Reported adverse
effects are headache, grandmal seizures, memory loss, gastrointestinal and dermatological
symptoms.
Applications: It is used as an intense sweetening agent in tablets, powder mixes and vitamin
preparations. It enhances flavor systems and can be used to mask some unpleasant taste and has
sweetening powder of 180-200 times that of sucrose.