CHAPTER V

DRUG,PLANT AND EXCIPIENT
PROFILES
DRUG, PLANT AND EXCIPIENT PROFILES

5.1 Drug profile
Propranolol HCl 4, 88
Propranolol HCl is a synthetic beta-adrenergic receptor blocking agent.
Structural formula:

Chemical Name: 2-Propanol, 1- [(1-methylethyl) amino] – 3 - (1-naphthalenyloxy)-,
Hydrochloride, (±).
Molecular formula: C16H21NO2 • HCl
Molecular weight: 295.80g/mol.
Melting point: 163ºC.
State/Form: Crystal.
Description: Almost odorless, bitter taste.

MAHARAJAH’S COLLEGE OF PHARMACYPage 43

PLANT AND EXCIPIENT PROFILES Solubility: Soluble in water and ethanol. leads to increase in the heart rate. Mechanism of action: The mechanism of the antihypertensive effect of Propranolol HCl has not been established. The mechanism of the anti migraine effect of Propranolol HCl has not been established. and this appears to be its principal antiarrhythmic mechanism of action. The net physiologic effect of beta-adrenergic blockade is usually advantageous and is manifested during exercise by delayed onset of pain and increased work capacity. which affects the cardiac action potential. but the β 2 (noncardiac) receptors may be involved. In angina pectoris. Factors that may contribute to the antihypertensive action include: (1) decreased cardiac output. it readjusts to or below the pre-treatment level with chronic use of Propranolol HCl. (2) inhibition of rennin release by the kidneys. The significance of the membrane action in the treatment of arrhythmias is uncertain. Although total peripheral resistance may increase initially. and the velocity and extent of myocardial contraction. Propranolol HCl generally reduces the oxygen requirement of the heart at any given level of effort by blocking the catecholamine induced receptors. should be stored at room temperature (15-30°C) and away from light. Beta-adrenergic receptors have been demonstrated in the pial vessels of the brain. end diastolic pressure. and (3) diminution of tonic sympathetic nerve outflow from vasomotor centers in the brain. Propranolol HCl exerts its anti-arrhythmic effects in concentrations associated with betaadrenergic blockade. In dosages greater than required for beta blockade. Storage conditions: Store in airtight containers. systolic blood pressure. and systolic ejection period. A central effect is also possible.CHAPTER V DRUG. The specific mechanism of Propranolol HCl antitremor effects has not been established. Propranolol HCl also exerts a quinidine like or anesthetics like membrane action. MAHARAJAH’S COLLEGE OF PHARMACYPage 44 . Effects of Propranolol HCl on plasma volume appears to be minor and somewhat variable. Propranolol HCl may increase oxygen requirements by increasing left ventricular fiber length.

Propranolol HCl is metabolized through three primary routes: aromatic hydroxylation (mainly 4hydroxylation). It has been estimated that the percentage contributions of these routes to total metabolism are 42%. The four major metabolites are Propranolol HCl glucuronide. However. Biological half life: 3 – 6 hr Metabolism Propranolol HCl is extensively metabolized with most metabolites appearing in the urine. half-life. Peak plasma concentrations occur about 1 to 4 hr after an oral dose. only about 25% of Propranolol HCl reaches the systemic circulation. it undergoes high first-pass metabolism by the liver and on average. naphthyloxylactic acid and glucuronic acid. The S (-) enantiomer is preferentially bound to α1 glycoprotein and the R (+) enantiomer preferentially bound to albumin. or the amount of unchanged drug in the urine. plasma binding. but with considerable variability between individuals. and is distributed into breast milk. The volume of distribution of Propranolol HCl is approximately 4litres/kg.PLANT AND EXCIPIENT PROFILES Pharmacokinetics Absorption Propranolol HCl is highly lipophilic and almost completely absorbed after oral administration. MAHARAJAH’S COLLEGE OF PHARMACYPage 45 . respectively. Distribution Approximately 90% of circulating Propranolol HCl is bound to plasma proteins (albumin and α1 acid glycoprotein). Administration of protein-rich foods increase the bioavailability of Propranolol HCl by about 50% with no change in time to peak concentration. and direct glucouronidation. Propranolol HCl crosses the blood-brain barrier and the placenta. N-dealkylation followed by further side-chain oxidation. The binding is enantiomer selective. and sulfate conjugates of 4-hydroxy Propranolol HCl.CHAPTER V DRUG. 41% and 17%.

It may be used alone or used in combination with other antihypertensive agents. Partial clearance of 4-hydroxy Propranolol HCl was significantly higher and of naphthyloxylactic acid significantly lowers in EMs than PMs.CHAPTER V DRUG. Angina pectoris due to coronary atherosclerosis Propranolol HCl tablets are indicated to decrease angina frequency and increase exercise tolerance in patients with angina pectoris. no difference was observed between CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) with respect to oral clearance or elimination half-life. Migraine MAHARAJAH’S COLLEGE OF PHARMACYPage 46 . 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. Atrial fibrillation Propranolol HCl tablets are indicated to control ventricular rate in patients with atrial fibrillation and a rapid ventricular response. Therapeutic indication Hypertension Propranolol HCl tablets are indicated in the management of hypertension. particularly thiazide diuretics.PLANT AND EXCIPIENT PROFILES Elimination In healthy subjects.

Generic. Inderal® (Wyeth-Ayerst) (Rx). The efficacy of Propranolol HCl in the treatment of a migraine attack that has started has not been established. 80 mg/ml concentrate in 30 ml. Propranolol HCl Intensol® (Roxane). 80 mg. Inderal® LA (WyethAyerst). (Rx) Propranolol HCl for Injection 1 mg/ml in 1 ml amps or vials. 120 mg. Propranolol HCl® (Roxane) (Rx) MAHARAJAH’S COLLEGE OF PHARMACYPage 47 . Betachron E-R® (Inwood). (Rx) Propranolol HCl Oral Solution 4 mg/ml. Generic. 8 mg/ml. 160 mg.CHAPTER V DRUG. and Propranolol HCl is not indicated for such use.PLANT AND EXCIPIENT PROFILES Propranolol HCl tablets are indicated for the prophylaxis of common migraine headache. Therapeutic dosage Propranolol HCl Extended/Sustained-Release capsules 60 mg.

White flowers appear in early summer and develop into long. slender. including India. The plant reaches a height of 0.2 Plant profile 87 Classification Trigonella foenum graceum(L) Kingdom: Plantae . MAHARAJAH’S COLLEGE OF PHARMACYPage 48 .Plants Subkingdom: Tracheobionta – Vascular Plants Super Division: Spermatophyta – Seed Plants Division: Magnoliophyta – Flowering Plants Class: Magnoliopxida . yellow brown pods. and the United States.8 meters and has trifoliate leaves. – Fenugreek P Species: Trigonella foenum graceum (L) – Cultivated Fenugreek P Group: Dicot Description: Fenugreek. Today. is an erect annual herb native to southern Europe and Asia. southern Africa.Dicotyledons Subclass: Rosidae Order: Fabales Family: Fabaceae – Pea Family Genus: Trigonella L. it grows in many parts of the world.CHAPTER V DRUG.3 to 0.PLANT AND EXCIPIENT PROFILES 5. Trigonella foenum-graceum (L).

59. anti. arthritis.121mg Ash (Total) .1% MAHARAJAH’S COLLEGE OF PHARMACYPage 49 .PLANT AND EXCIPIENT PROFILES Fenugreek seeds are hard.inflammatory.48% Niacin . antiseptic.68/g Fat .4% Phosphorus . yellowish brown and angular with a side of about 3mm (1/8 angstroms). Aluminum .1. General Information of Fenugreek It is an Asiatic herb with aromatic seeds.CHAPTER V DRUG.8. It is one of the primary supplements used to support type II diabetes. Properties: Anticardiarrhal. The seeds are rich in proteins and contain about 50% fiber and 25% soothing mucilage.288mg Carbohydrates .9% Crude Fiber .3.73mg Dietary Fiber . and digestive problems.35mg Cobalt . In ancient china herbalists used it for problems of kidney and male reproductive tracts. These seed may benefit people suffered from various conditions such as wounds. Nutritional profile: Fenugreek seeds were calculated on a zero moisture basis per 100g.21mg Calcium . abscesses. People may roast the seeds or store them as dried seeds. bitter expectorant. It is used worldwide as a spice as well as medicinal herb to soothe the stomach and help to maintain the blood sugar levels.0.7% Manganese .0.0.6mg Calories . bronchitis.182mg Magnesium .6.

High doses of fenugreek seeds may cause gastro.32mg Sodium – 58mg Vitamin A .47mg Riboflavin – 0. These two elements are thought to account for many benefits of fenugreek.25mg Silicon – 0.5 IU Vitamin C – 60mg Sugars – 13% Starch – 15% Fenugreek benefits Fenugreek seeds are rich source of trigonelline.38. MAHARAJAH’S COLLEGE OF PHARMACYPage 50 . Studies have shown that fenugreek helped lower cholesterol.PLANT AND EXCIPIENT PROFILES Iron – 5.6mg Potassium – 102mg Chromium – 0.6% Thiamine – 1.CHAPTER V DRUG. pregnant women should avoid fenugreek. Fenugreek side effects Fenugreek appears to be safe at low doses. blood sugar levels in patients suffered from diabetes. Fenugreek may stimulate uterine.04mg Protein – 13. The steroidal saponins may inhibit the cholesterol absorption and synthesis while fiber is thought to help lower sugar levels.intestinal disturbances and nausea. lysine and l – tryptophan and they also contain a large amount of steroidal saponins and fibers.

3 Sodium Starch Glycolate 89 Structural formula: Synonyms: Explotab.CHAPTER V DRUG. Description: MAHARAJAH’S COLLEGE OF PHARMACYPage 51 .PLANT AND EXCIPIENT PROFILES 5. Primogel Chemical names: Sodium carboxymethyl starch Non proprietary Name: BP: Sodium starch glycolate Functional category: Tablet and capsule disintegrant.

Kollidon CL. Applications: As a disintegrant in tablet (wet granulation and direct compression) and capsule formulation in 2-8% concentration. odourless. 5. Polyvinylpolypyrrolidone homopolymer. Safety: It is generally regarded as a non-toxic and non-irritant material. It should be stored in a well closed container to protect from wide variations in humidity and temperature that may cause cracking. oral ingestion of large quantities may be harmful. It consists of oval or spherical granules. Polyplasdone XL-10. In water it swells up to 300 times its volume. However. sparingly soluble in ethanol (95%). Polyplasdone XL. free flowing powder. tasteless.4 Crospovidone 89 Structural formula: Synonyms : Crosslinked povidone.PLANT AND EXCIPIENT PROFILES Sodium starch glycolate is a white to off-white.CHAPTER V DRUG. E1202. 30-100μm in diameter with some less spherical granules ranging from 10-35μm in diameter. Solubility: Practically insoluble in water. and 1- vinyl-2-pyrrolidinone . Stability and storage conditions: It is a stable material. Kollidon CL-M. Incompatibilities: Incompatible with ascorbic acid. MAHARAJAH’S COLLEGE OF PHARMACYPage 52 (PVPP).

Colloidal Silica. USPNF: Crospovidone Empirical formula and molecular weight: (C6H9NO) n >1000. with little tendency to form gels. Cab-O-Sil M-5P. finely divided. Stability and storage conditions: Since crospovidone is hygroscopic. Studies suggest that the particle size of crospovidone strongly influences disintegration of analgesic tablets.PLANT AND EXCIPIENT PROFILES Chemical name: 1-Ethenyl-2-pyrrolidinone homopolymer Non-proprietary Names: BP. Crospovidone can also be used as a solubility enhancer. Functional category: Tablet disintegrant. practically tasteless. free-flowing.Crospovidonum. 5.5 Colloidal Silicon Dioxide 89 Synonyms: Aerosil. An exact determination of the molecular weight has not been established because of the insolubility of the material. Chemical Name: Silica. PhEur. Nonproprietary Names: MAHARAJAH’S COLLEGE OF PHARMACYPage 53 .Crospovidone.CHAPTER V DRUG. odorless and hygroscopic powder. Hochdisperses Silicum Dioxid. Fumed Silicon Dioxide. Description: Crospovidone is a white to creamy-white. Fumed Silica. It rapidly exhibits high capillary activity and pronounced hydration capacity. Applications in pharmaceutical formulation or technology: Crospovidone is a water-insoluble tablet disintegrant and dissolution agent used at 2–5% concentration in tablets prepared by direct compression or wet and dry granulation methods. dry place. it should be stored in an air tight container in a cool.

and acids. Description: Colloidal silicon dioxide is submicroscopic fumed silica with a particle size of about 15nm.46 Solubility: practically insoluble in organic solvents. When used in aqueous system at a pH 0-7.5. water. 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. viscosity-increasing agent. Empirical Formula: SiO2 Molecular weight: 60. MAHARAJAH’S COLLEGE OF PHARMACYPage 54 . Colloidal silicon dioxide powder should be stored in a well-closed container. soluble in hot solutions of alkali hydroxide.08 Functional Category: Adsorbent. glidant suspending agent. amorphous powder. tablet disintegrant. except hydrofluoric acid.Solubility in water is 150mg/L at 258ºC (pH 7) Specific gravity: 2. it is a light. odorless.PLANT AND EXCIPIENT PROFILES BP: Colloidal Anhydrous Silica. Typical Properties: Melting point: 160ºC Refractive index: 1.2 Stability and Storage Conditions: Collodial silicon dioxide is hygroscopic but adsorbs large quantities of water without liquefying. loose. JP: Light Anhydrous Silicic Acid. thermal stabilizer. tasteless. USP-NF: Colloidal Silicon Dioxide. anticaking agent. PhEUR: Silica. Collidal Anhydrous.CHAPTER V DRUG. emulsion stabilizer. bluish-white-colored. forms a colloidal dispersion with water.

Applications:  It is used to stabilize emulsions and as a thixotropic thickening and suspending agent. MAHARAJAH’S COLLEGE OF PHARMACYPage 55 . 5.  It is used to promote particulate suspension. USP-Microcrystalline cellulose.PLANT AND EXCIPIENT PROFILES Handling Precautions: Eye protection and gloves are recommended. 102 Chemical names: Cellulose Non-proprietary name: NF-Microcrystalline cellulose. 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.CHAPTER V DRUG. and minimize the clogging of spray nozzles. eliminate hard settling.6 Microcrystalline cellulose 89 Structural formula: Synonyms: Cellulose gel: Crystalline cellulose: Avicel PH 101.  It is used as a tablet disintegrant and as an adsorbent dispersing agent for liquids in powders.

slightly soluble in 5% w/v NaOH solution. hygroscopic. partially depolymerised cellulose occurs as a white. tablet disintegrant.5 to 20% Tablet disintegrant . Store in a well closed container.PLANT AND EXCIPIENT PROFILES Empirical formula: (C6H10O5) n = 220 Molecular weight: 36.) Functional category: Tablet and capsule diluent. 5. Description: Purified.5 to 20%. tasteless. odorless. crystalline powder composed of porous particles. Incompatibilities: None cited in the literature Safety: Generally regarded as safe. dilute acids and most organic solvents.5 to 15% Tablet glidant .000(approx. Stability and storage conditions: Stable.5 to 15% Antiadherent .7 Magnesium stearate 89 Structural formula: MAHARAJAH’S COLLEGE OF PHARMACYPage 56 . suspending and/or viscosity increasing agent. In formulation of tablets: Tablet binder/diluent (wet or dry granulation) . Applications: It has following applications in tablet formulations. Solubility: Insoluble in water.CHAPTER V DRUG.

alkalies. having a faint characteristic odour and taste.Magnesium stearate. Stability and storage conditions: Stable.3 Functional category: Tablet and capsule lubricant. BP/EP. magnesium salt.Magnesium stearate. impalpable powder of low bulk density. The powder is greasy to touch and readily adheres to the skin. Incompatibilities: Incompatible with strong acids. ether and water. Chemical names: Octadecanoic acid. non-self polymerizable. iron salts and with strong oxidising materials. Store in a cool. magnesium stearate Non-proprietary name: NF. Solubility: Practically insoluble in ethanol (95%).PLANT AND EXCIPIENT PROFILES Synonyms: Metallic stearic. MAHARAJAH’S COLLEGE OF PHARMACYPage 57 . precipitated or milled. Empirical formula: C36H70MgO4 Molecular weight: 591. dry place in a well closed container. magnesium salt. slightly soluble in benzene and warm ethanol (95%). white.CHAPTER V DRUG. Description: It is a fine.

Aspartyl phenylamine methyl ester.PLANT AND EXCIPIENT PROFILES Safety: Described as inert or nuisance dust.25 to 2. Osha has adopted limits of 15mg/m 3 for the total dust and 5mg/m3 for the respirable fraction. Degradation also occurs during prolonged heat treatment. MAHARAJAH’S COLLEGE OF PHARMACYPage 58 . sparingly soluble in water. glidant and antiadherent in the concentration range of 0. However. in a cool. dry place. Description: It occurs as white and almost odourless crystalline powder. Nutrasweet. Bulk material should be stored in a well-closed container. 5. Functional category: Sweetening agent.8 Aspartame90 Synonyms: APM. IP – Aspartame. Chemical name: L-aspartic acid.Eur – Aspartamum. oral consumption of large quantities may result in some laxative effect or mucosal irritation. Dust clouds of magnesium stearate may be explosive.CHAPTER V DRUG. hydrolysis occurs. Tri-sweet. L-phenylalanine Non proprietary name: USP – Aspartame. Applications: Tablet and capsule lubricant.0%. In presence of moisture. Stability and Storage Conditions: It is stable in dry conditions. Ph. Sanecta. solubility increases at higher temperature and at more acidic pH. BP – Aspartame. Canderel. Solubility: Slightly soluble in ethanol (95%).

powder mixes and vitamin preparations. memory loss. grandmal seizures.CHAPTER V DRUG. It enhances flavor systems and can be used to mask some unpleasant taste and has sweetening powder of 180-200 times that of sucrose. Applications: It is used as an intense sweetening agent in tablets. gastrointestinal and dermatological symptoms.PLANT AND EXCIPIENT PROFILES Safety: The WHO has set an acceptable daily intake of 40 mg/kg body weight. Reported adverse effects are headache. MAHARAJAH’S COLLEGE OF PHARMACYPage 59 .