Disintegration test (U.S.P.)

Disintegration test is an official test. It is the time required for the tablet to break into particles, the disintegration test is a measure only of the time required under a given set of conditions for a group of tablets to disintegrate into particles.It is performed to identify the disintegration of tablet in particular time period. Disintegration test is not performed for controlled & sustained release tablets.

The U.S.P. device to test disintegration uses 6 glass tubes that are 3” long; open at the top and 10 mesh screen at the bottom end. To test for disintegration time, one tablet is placed in each tube and the basket rack is positioned in a 1-L beaker of water, simulated 

gastric fluid or simulated intestinal fluid at 37 ± 2⁰C such that the tablet remain 2.5 cm below the surface of liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in their downward movement. 

Move the basket containing the tablets up and down through a distance of 5-6 cm at a frequency of 28 to 32 cycles per minute. Floating of the tablets can be prevented by placing perforated plastic discs on each tablet.

According to the test the tablet must disintegrate and all particles must pass through the 10 mesh screen in the time specified. If any residue remains, it must have a soft mass.

Liquids used in disintegration

a)     Water

b)     Simulated gastric fluid (pH = 1.2 HCl),

c)       Simulated intestinal fluid (pH = 7.5, KH₂PO₄ (phosphate buffer) + pancreatic enzyme + NaOH)

Disintegration testing conditions and interpretation

S.	Type of tablets	Medium	Temp.	limit
1	Compressed uncoated		37 ± 2 0C	15 minutes or as per individual monograph
2	Sugar coated If 1 or 2 tablets fail	Water 0.1 N HCL	37 ± 2 0C	60 minutes or as per individual monograph
3	Film coated	water	37 ± 2 0C	30 minutes or as per individual monograph
4	Enteric coated	0.1 N HCL & Phosphate buffer pH 6.8	37 ± 2 0C	1 hr or as per individual monograph
5	Dispersible/ Effervescent	water	37 ± 2 0C	LST < 3 minutes or as per individual monograph
6	Buccal tablets		37 ± 2 0C	4 hr or as per individual monograph

U.S.P. method for uncoated tablets:

Start the disintegration test on 6 tablets. If one or two tablets from the 6 tablets fail disintegrate completely within 30min repeat the same test on another 12 tablet. (i.e. the whole test will consume 18 tablets). Not less than 16 tablets disintegrate completely within the time. If more than two tablets (from the 18) fail to disintegrate, the batch must be rejected.

For Coated tablets:

To remove or dissolve the coat, immerse the tablet in distilled water for 5min. Put the tablet in the apparatus in water or HCL for 30 min at 37^oC (according to the U.S.P). If not disintegrated, put in intestinal fluid. If one or two tablets fail to disintegrate, repeat on 12 tablets. So 16 tablets from the 18 must completely disintegrate within the time, if two or more not disintegrated the batch is rejected.

U.S.P. and B.P Method for Enteric coated tablets:

1. Put in distilled water for five minutes to dissolve the coat.

2. Then put in simulated gastric fluid (0.1M HCL) for one hour.

3. Then put in simulated intestinal fluid for two hours.

If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the patch must be rejected.

Dissolution Test for tablets

Dissolution is an official test. Dissolution is performed to check the percentage release from the dosage forms like tablets. Tablet breaks down into small particle which offers a greater surface area to the dissolving media. Disintegration test does not give assurance that particles will release drug in solution at an appropriate rate, that’s why dissolution tests & it is specifications developed for all tablet products.

1. USP Dissolution apparatus I (Basket method)

A single tablet is placed in a small wire mesh basket attached to the bottom of the shaft connected to a variable speed motor. The basket is immersed in a dissolution medium (as specified in monograph) contained in a 1000 ml flask. The flask is cylindrical with a hemispherical bottom. 

The flask is maintained at 37 ± 0.5⁰C by a constant temperature bath. The motor is adjusted to turn at the specified speed and sample of the fluid are withdrawn at intervals to determine the amount of drug in solutions.

USP Dissolution apparatus II (Paddle method)

It is same as apparatus-1, except the basket is replaced by a paddle. The dosage form is allowed to sink to the bottom of the flask before stirring. 

For dissolution test U.S.P. specifies the dissolution test medium and volume, type of apparatus to be used, rpm of the shaft, time limit of the test and assay procedure for. The test tolerance is expressed as a % of the labeled amount of drug dissolved in the time limit. 

Haemostasis and Fibrinolysis

Hemostasis is the arrest of bleeding from damaged blood vessels. It is complex cascade of enzymatic reactions.

Natural clotting limitation factors are heparin and antitrombin IIII Fibrinolysis is lysis of thrombus for restoration of blood flow:

Pathology of haemostasis and fibrinolysis: ·

1.     Decrease in blood coagulation and (or) increase in fibrinolysis causes      bleeding.
2.      Increase in blood coagulation and (or) decrease in fibrinolysis causes          thrombosis, thromboembolism, syndrome of desseminated intravasal blood    coagulation.

Drugs affecting blood coagulation and fibrinolysis

 1. Coagulants (They increase blood coagulation)

 2. Anticoagulants (They decrease blood coagulation)

 3. Anti-platelet drugs (They decrease platelet aggregation)

 4. Fibrinolytic drugs (They increase fibrinolysis)

 5. Inhibitors of fibrinolysis (They decrease fibrinolysis)

Drugs affecting fibrinolysis

Classification

        I.            Fibrinilytic drugs

a)     Direct-acting: Fibrinolysin

b)     Indirect-acting (activators of profibrinolysin)

a)     Non-selective: Streptokinase, Streptoliase

b)     Selective: Alteplase

      II.            Inhibitors of fibrinolysis

a)     Direct –acting: Contrical

b)     Indirect- acting: Aminocaproic acid,  Amben

FIBRINOLYSIN

It is protein from donors’ plasma, the active factor of fibrinolysis & administered by IV infusion. It has direct action on fibrin and dissolves fibrin clot in the first hours after thrombosis. It is used for treatment of acute thrombosis, acute miocardial infarction, thrombophlebitis. It may cause bleeding resulting from increase in fibrinilysis, allergy, anaphylaxis, arrythmia, hypotension.

Contraindications: bleeding, cerebral vascular accident, recent trauma of brain, surgery, uncontrolled hypertension.

activators of fibrinolysis

steptokinase

It is the proteolytic enzyme from haemolytic streptococcus. It acts indirectly, inhibits the conversion of plasminogen to plasmin & degradation both of fibrin and fibrinogen to systemic activation of fibrinolysis and dissolving of thrombus.  Plasma half-life is 23 min; is administered by IV infusion (intracoronary infusion in myocardial infarction). It is more active than fibrinolysin, does not cause arrhythmia.

Alteplase (ACTILISE)

It is tissue plasminogen activator, product of biotechnology, half-life is 5 min& is administered by IV infusion. It has high affinity for fibrin and selectively acts only on plasminogen, bound with thrombus.

Inhibitors of fibrinolysis

Contrical (Aprotinin)

It is direct acting inhibitor of fibrinolysis and proteolysis & administered IV slowly or by IV infusion.It binds with plasmin and inactivates it, inhibits activity of trypsin and kallikrein. It inhibits fibrinilysis and decreases bleeding caused by activation of fibrinolysis; inhibits proteolysis and inflammation.

indications: bleeding resulting from activation of proteolysis, myocardial infarction, acute pancreatitis, prophylaxis of proteolytic complications after surgeries on pancreas, thyroid glands, prevention of proteolysis activation after the surgery on bigger salivary glands; paradontitis (topically)

 Side-effects: allergy, nausea, vomiting, hypotension, tachycardia

Aminocaproic acid

It  is indirect-acting inhibitor of fibrinolysis & administered orally and by IV infusion, acts during 4-6 hr, is not metabolized and excreted with urine.It  interacts with plasminogen and inhibits its transformation into plasmin, particularly inhibits plasmin; inhibits proteolytic enzymes and kallikrein. It inhibits fibrinolysis and decreases bleeding caused by the activation of fibrinolysis; suppresses proteolysis, decreases inflammation, has anti-allergic action, stimulates antitoxic function of the liver.

Indications: They are similar to the same to contrykal and also syndrome of dessemenated intranasal blood coagulation, obstetrics pathology (ablation placenta, uterine haemorrhages), liver diseases, hypoplastic anaemia.It is use in dentistry is applied topically to treat parodontitis and to stop bleeding from dental root channels.

Side-effects: Dizziness, hypotension, bradycardia, arrhythmia, skin rash, vomiting , nausea.

Pharmacist

Pharmacists, also known as chemists or druggists, are healthcare professionals who practice in pharmacy, the field of health sciences focusing on safe and effective medication use. A pharmacist is a member of the health care team directly involved with patient care. Pharmacists undergo university-level education to understand the biochemical mechanisms and actions of drugs, drug uses, therapeutic roles, side effects, potential drug interactions, and monitoring parameters. This is mated to anatomy, physiology, and pathophysiology. Pharmacists interpret and communicate this specialized knowledge to patients, physicians, and other health care providers.

Among other licensing requirements, different countries require pharmacists to hold either a Bachelor of Pharmacy, Master of Pharmacy, or Doctor of Pharmacy degree.

Dispensing is an integral service provided by pharmacists as part of the Medication Management Cycle. The separation of prescribing and dispensing of medicines provides a safety mechanism as it ensures independent review of a prescription occurs prior to the commencement of treatment.

Medication Management Cycle

Step 1: The pharmacist will ask if you have visited this pharmacy before. If the answer is ‘No’, you will be asked to fill out a consent form. This allows the pharmacist to fill your prescription. If the answer is ‘Yes’, they will ask for an identifier (birthday or home address). This allows for an easy search within the pharmacy's computer system for your prescription records. You will then be asked if you have had this medication before, and what it is being used to treat. This information will allow the pharmacist to personalize your medication counsel when the medication is picked up.

Step 2: A Pharmacy technician will enter the prescription into your profile, checking the: doctor’s information, medication/dose, indications from the prescriber, and quantity of the script. The pharmacy system will check for possible interactions or other potential issues through the Nova Scotia Drug Information System.

Step 3: The medication bottle will be scanned and packaged with the Lot and Expiry. The medication is then counted for the designated quantity, labelled and handed off to the pharmacist to be checked.

Step 4: The pharmacist will perform a check of your medication, reviewing previous usage (if any), and information entered at the beginning work station. They will also print off counselling documents to provide the patient with more information on the medication.

Step 5: The patient will pick up their medication and have a quick conversation with the pharmacist to ensure proper communication and compliance.

A prescription (symbol: ℞, representing the Latin imperative verb, recipe = take, take thou) is a health-care program implemented by a physician or other qualified health care practitioner in the form of instructions that govern the plan of care for an individual patient.[1] The term often refers to a health care provider's written authorization for a patient to purchase a prescription drug from a pharmacist.

The prescription gives the pharmacist details about the required prescription medicine including:

1.      The name of the medicine (its active ingredient name and/or brand name)

2.      Whether or not brand substitution is allowed – that means, if the pharmacist can give you an alternative brand of your medicine that contains the same active ingredient

3.      The form of your medicine – for example, tablets, liquid or cream

4.      The strength of your medicine – for example, 75 milligrams (mg) per tablet or 75 mg per millilitre (ml) of liquid

5.      Dosage of medicine you need to take – for example, one tablet once daily

6.      Other instructions for taking the medicine – for example, how long you need to take it for

7.      Quantity of medicine required – for example, 40 tablets

8.      Number of repeat prescriptions, if any, to be filled once the current prescription runs out.