Pharmaceutical Calculations, Powders & Liquid Dosage Forms

Chapter 2

Pharmaceutical Calculations, Powders & Liquid Dosage Forms 

Pharmaceutical Calculation 

Metrology

While dispensing of drug it is desirable for a pharmacist to have thorough knowledge regarding weights and measures which are used in calculations. There are two types of system for weights and measures:

1. Imperial system 

2. Metric system

1. Imperial System

This is an old system of weights and measures. Weight is a measure of the gravitational force acting on a body and is directly proportional to mass. The imperial system is divided in two parts for the purpose of measurement of weights. These are

 (a) Avoirdupois system. 

(b) Apothecaries' system.

2. Metric System

The metric system is used for the measurement of weight and capacity. The metric system in India was implemented from 1st April 1964 in pharmacy profession. This system was used the Indian pharmacopoeia. The metric system is an alternative system of measurement used in most countries, as well as in the United States. The metric system is based on joining one of a series of prefixes, including kilo-, hector-, deka-, Deci-, centi-, and milli-, with a base unit of measurement, such as meter liter, or gram.

Calculation of Isotonic

• 1. Freezing Point Method

• The lachrymal secretion contains several solutes in it and has a freezing point of -0.52°C. All solutions, which freeze at -0.52°C, will be isotonic with the lachrymal fluid. Human blood plasma also freezes at this temperature and hence solutions having freezing point at -0.52°C will be isotonic with blood plasma as well. Adjustment of tonicity is simplified if the freezing points of the medicament and the inert salt (adjusting substance) are known for various strengths of their solutions. Freezing points are usually expressed in terms of 1% solutions and one can calculate the quantity by multiplying the freezing point with the factor.

Example:

• How much boric acid is required to render 200 ml of eyewash containing 1% boric acid are to be dispensed. (F.P. of 1% boric acid at -0.29°C and E.P. of 1% solution of sodium chloride = -0.58°C). Applying the above equation: Thus the working formula for 200 ml of the eyewash will be: Boric acid (1%, for 200 IL) = 19 x 2 = 2 g. Sodium chloride (0.39%, for 200 ml) = 0.39 x 2 = 0.78 g. Purified water q.s. 200 ml.

solution:

• However if the pharmacist has been asked to supply 200 ml of eyewash of boric acid, the calculation will be as follows: Lowering of 0.29°C in F.P. is caused by 1 g of boric acid Lowering of 0.52°C in F.P. will be caused by 1.8 g of boric acid Therefore, 1.8 g of boric acid is required to make 100 ml of eyewash and the working formula will be : Boric acid (1.8%, for 200 ml) = 1.8 x 2 = 3.6 g. Purified water, q.s. 200 ml.

Proof Spirit

Proof spirit:

•  Proof spirit is defined as a mixture of absolute alcohol and water which has 57.1% v/v ethyl alcohol. The strength of alcoholic preparations are indicated by degrees 'over proof' and 'under proof' for excise purpose. Proof spirit is that mixture of alcohol and water which at 51° F weighs 12/13th of an equal volume of water. In India 57.1 volume of ethyl alcohol is considered to be equal to 100 volumes of proof spirit. This means that alcoholic solutions containing 57.1%v/v alcohol is a proof spirit which is said to be 100 proof. So any strength above proof strength is expressed as over proof (O.P.) and any strength below proof strength is expressed as under proof (U.P.).

• Formula for calculation of over proof and under proof:

• Formula for calculation of over proof and under proof: (0) 57.1% v/v alcohol = 100 volume of proof spirit. Therefore, 1% v/v alcohol = 100/57.1 = 1.753 volume of proof spirit. (ii) So multiply the given percentage strength of alcohol by 1.753 and deduct from the product (iii) If the result is positive it is known as over proof. (iv) If the result is negative, it is known as under proof.

power 

• A powder is a homogeneous mixture of more or less finely divided particle or material in dry form. It is a solid dosage form of medicament which are meant for internal and external uses. They are present in crystalline and amorphous form.

Advantages

• They impart flexibility with regard to a wide selection of drugs. They are stable when compared to other dosage forms. They show rapid therapeutic effect. Ease in administration to all categories of patients. 

• They are economical because they do not require special technique or machinery. Chances of incompatibility are less. 

Disadvantages

• Drugs having bitter, nauseous and unpleasant taste cannot be dispensed in powdered form. Deliquescent and hygroscopic drugs cannot be dispensed in powdered form. Drugs which get affected by atmospheric conditions are not suitable for dispensing in powder form.

General Method of Preparation

• The crystalline substances are powdered separately and then weigh the required quantity of each ingredient. Mix all ingredients in ascending order of their weight. Mix thoroughly to obtain homogeneous mixture. Weigh required number of powders and wrap in the papers. The hygroscopic and deliquescent and volatile substance requires to be double wrapped. The inner wrapper should be wax paper so as to prevent volatilization.

Types of powders

• 1. Divided Powders 2. Bulk Powder (a) Simple Powder a) Dusting Powder (b) Compound powder (b) Effervescent Powder c) Dentifrices d) Insufflations e) Douche Powder (f) Snuffs.

Dusting Powder 

• A powder is used on skin to relieve irritation or absorb moisture and to keep skin soft and comfortable. Dusting powders are used externally for local application not intended for systemic action. They are applied to various part of body as lubricants, protectants, absorbents, antiseptics, astringent and antiperspirant. Dusting powders always should be dispensed in a very fine state of subdivision to enhance effectiveness and minimize irritation. When necessary, they may be passed through 80, 100, number sieves.

Effervescent Powder 

• They are specially prepared solid dosage form of medicament meant for internal use. They contain medicament (API) mixed with citric acid, tartaric acid and sodium bicarbonate. Saccharine may be added as sweetening agent. Before administration the desired quantity is dissolved in water, the acid and bicarbonate react together producing effervescence (releasing CO2). This mixture should be taken while effervescing.

Dentifrices (Tooth Powder) 

• Dentifrices are bulk powders used to clean teeth. They contain a soap or detergent (for cleaning action), mild abrasive and an anti-cryogenic agent Mild abrasion can be provided by using finely precipitated Calcium Carbonate, Sodium Chloride, Magnesium Chloride etc. A strong abrasive substance should not be used as it may cause damage to the tooth. They are applied with the help of toothbrush for cleaning the surface of teeth.

Formula:

• RX For 100 gm tooth powder Hard soap, fine powder - 5 gm Precipitated calcium carbonate - 94 gm Saccharine sodium - 2 gm Peppermint oil - 4 gm.

Insufflations 

These are finely divided powders introduced into body cavities such as the ear, nose, throat, tooth sockets and vagina. An insufflators is employed to administer these products. It sprays the powder into a stream of finely divided particles all over the site of application. Pressure aerosols also have been employed as a means of administering insufflations, especially for potent drugs.

Snuffs 

• These are finely divided solid dosage form of medicament which are inhaled into nostrils for its antiseptic, bronchodilator and decongestion actions. Traditionally, it is sniffed or inhaled lightly after a pinch of snuff is either placed onto the back surface of the hand, held pinched between thumb and index finger, or held by a specially made "snuffing" device. Snuff comes in a range of texture and moistness, from very fine to coarse, and from toast (very dry) to very moist.

Liquid Dosage Form 

• The use of liquid pharmaceuticals has been justified on the basis of ease of administration and rapid and efficient absorption of drug.

• Dosage forms meant either for internal, external or parenteral use may be sub-classified into monophasic or biphasic liquid dosage forms. The monophasic liquid dosage forms consist of either true or colloidal solutions or solubilized system. All these consists of only a single phase and may have either aqueous or non-aqueous solvents as the base. Biphasic dosage forms are represented by emulsions and suspensions and consist of two immiscible phases, the continuous phase and the dispersed phase. The continuous phase in both is a liquid, the dispersed phase in emulsions is also a liquid while in case of suspensions, the dispersed phase consists of a finely divided solid. The classification of liquid dosage form is given in and the comparison of characteristics of various liquid dosage forms are shown in Table. 

Advantages of Liquid Dosage Forms 

• The presentation of drugs as liquid dosage form offers the following advantages:

• (0) The drug is more readily available for absorption from liquid dosage forms as compared to solid dosage form. By providing the drug in solution, the dissolution phase of the absorption process can be surpassed, providing faster therapeutic response.

• (ii) The doses of drugs can be easily adjusted according to the need of the patient. If the dose of active ingredient is to be altered, a simple adjustment to the quantity of solution to be taken is all that is required.

Disadvantages of Liquid Dosage Forms:

• Drugs are usually less stable in liquid dosage forms as compared to solid dosage forms like tablets and capsules, particularly if they are susceptible to hydrolysis.

• (ii) Liquids, especially aqueous preparations, are susceptible to microbial contamination.

• (ii) Masking the unpleasant taste of a drug in solution is more difficult than when the drug is in a solid dosage form.

• (iv) Liquid preparations are usually bulky and therefore inconvenient to store and carry. Liquid dosage forms are always much larger and more bulky than solid formulations. Coupled with this is the fact that pharmaceutical liquids are packed in glass bottles, which are prone to breakage.

Excipients used in Formulation of Liquid Dosage Forms 

Sweetening agent:

• Sweeteners are indispensable components of many liquid oral dosage forms, especially those containing bitter or other unacceptable tastes. In fact, sweetening agents may comprise large portions of solid content in most liquid oral dosage forms. Sweeteners are often classified as either nutritive (caloric) or non-nutritive (non-caloric). Non-caloric sweetening agents are preferred for diabetic patients, as ingestion does cause increase in systemic glucose concentrations. Some of the most commonly used sweeteners include sucrose, sorbitol, mannitol, liquid glucose, honey molasses, saccharin, aspartame, sucralose, and acalypha-K. The types and concentrations of sweeteners for common prescription liquid medications are reported by Hill, Flaitz, and Frost. Sucrose is the most widely used sweetener, with a long history of use. It is a wh crystalline powder, soluble in water and alcohol. It inhibits the growth of microorganisms in solution at sucrose concentrations above 65 wt% by reducing the water-activity coefficient. Official simple syrup is an 85%w/V solution of sucrose in water. During the preparation of sucrose solution, care should be taken to avoid charring and caramelization caused by heat. Sucrose is chemically and physically stable in the pH range of 4.0-8.0. It is frequently used in conjunction with sorbitol, glycerin, and other polyols, which reduces its tendency to crystallize.

Solubility 

• Solubility is defined as amount of solute that can be dispersed molecularly in the given amount of solvent under standard conditions of temperature, pressure and ph. The following questions related to solubility must be resolved before formulating solution dosage form:

• (a) Will the drug(s) dissolve in the vehicle?

•  (b) How much drug will dissolve?

•  (c) How long will dissolution take? 

• (d) What is optimum pH for dissolution?

•  To determine the solubility of solute in solvent following points are to be considered: 

• (a) Temperature must be controlled.

• (b) The solute and the solvent should be pure. 

• (c) A saturated solution of the solute should be prepared before withdrawing the sample for analysis.

•  (d) A proper method of separation of saturated solution from the undissolved solute. 

• (e) Dissolved solute should be determined adequately by the suitable method of analysis.

Techniques of Solubilization

• In liquid pharmaceuticals solutions sometime, the active drug is poorly soluble or insoluble in desired solvent and could not be able to achieve the required concentration of formulation. In such cases, it is required to increase the solubility of that material in the solvent by a suitable technique. Solubilization is the technique by which the desired solubility of a poorly water-soluble substance is achieved. Since, water is the most commonly used solvent in pharmaceutical liquids, the following techniques have been aimed at increasing the solubility of a drug substance in water.

• Pharmaceutical Approach

1. pH Adjustments

• Most of the drugs are either weak acids or weak bases. The aqueous solubility of a weak acid or a weak base is greatly influenced by the pH of the solution. Hence, the solubility of drug that is either a weak base or a weak acid may be altered by adjusting the pH of the solution. The solubility of a weak base can be increased by lowering the pH of its solution whereas the solubility of a weak acid can be improved by increasing the ph. pH adjustment for improving the solubility can be achieved in two ways: 

• (a) Salt formation. 

• (b) Addition of buffers to the formulation. However, pH adjustments should be done judiciously since other factors such as stability, bioavailability, etc. can also be affected by a change in ph.

2. Cosolvency

• Cosolvency is the technique of increasing the solubility of poorly soluble drugs in a liquid by addition of a solvent miscible with the liquid in which the drug is also highly soluble. Cosolvents such as ethanol, glycerol, propylene glycol or sorbitol decreases the interfacial tension or alter the dielectric constant of the medium and increases the solubility of weak electrolytes and non-polar molecules in water. Example: Formulation of Diazepam injection using propylene glycol as cosolvent.

3. Complexation

• In certain cases, it may be possible to increase the solubility of a poorly soluble drug by allowing it to interact with a soluble material form a soluble intermolecular complex. It is however essential that the complex formed is easily reversible so that the free drug is released readily during or before contact with biological fluids. A number of compounds, such as nicotinamide and Beta-cyclodextrin, have been investigated as possible agents to increase the solubility of water insoluble drugs.

4. Surface active agent

• A surface-active agent is a substance which reduces the interfacial tension between the solute and the solvent to form thermodynamically stable homogeneous system. The mechanism involved in this solubilization technique involves micelle formation and due to formation of stable system it is widely used in pharmaceutical formulations. When a surfactant having a hydrophilic and a lipophilic portion is added to a liquid, it first accumulates at the air/solvent interface; further addition leads to its dispersion throughout the liquid bulk. At a certain concentration known as the Critical Micelle Concentration (CMC), the dispersed surfactant molecules tend to aggregate into groups of 100 to 150 molecules known as micelle.

5. Hydrotropism

• Hydrotropism is the term used to describe the increase in aqueous solubility of a drug by the use of large concentrations (20% to 50%) of certain additives. The exact mechanism for hydrotropism is not clear although complexation, solubilization or solvency have been suggested as the probable mechanisms. Hydrotropism is rarely applied to pharmaceutical formulations, as the increase in aqueous solubility is generally inadequate.