Pharmaceutical Technology I PDF

# Pharmaceutical Technology I ## Topical Solutions and Extracts * **Dr Dhiya Altememy** * **PhD in pharmaceutics** ## Miscellaneous oral solutions: Linctuses In addition to conventional solutions, syrups and elixirs, there are solution-based dosage forms that are administered orally, in particul...

# Pharmaceutical Technology I ## Topical Solutions and Extracts * **Dr Dhiya Altememy** * **PhD in pharmaceutics** ## Miscellaneous oral solutions: Linctuses In addition to conventional solutions, syrups and elixirs, there are solution-based dosage forms that are administered orally, in particular linctuses. This is briefly described below. * Linctuses are viscous liquid oral preparations that are prescribed for relief of cough. It normally consists of a simple solution of the active agent in a high concentration of sucrose, often with other sweetening agents. This type of product, which is also designed to be administered in multiples of 5 mL, should be sipped slowly and not be diluted beforehand with water to have the maximum and prolonged effect of medicament. Linctuses normally do not have any major side effects. In case of overdose, they may cause headache, stomach upset and diarrhea. * Formulation of linctuses requires the following: * **Vehicles:**Simple syrup is commonly used as the vehicle. Syrup tolu is preferred in certain cases because of its aromatic odor and flavor. Moreover, it is believed to have a mild expectorant action. * **Adjuvants:** * **Chemical stabilizers:**The stability of linctuses is due to the presence of the simple syrup as vehicle. * **Coloring agents:**Coal tar dyes * **Flavoring agents:**Lemon syrup, black current syrup, oxymel * **Preservatives:**Syrup has high osmotic pressure, which eliminates additional use of other preservatives. **Example: Codeine linctus BPC** | Ingredient | Quantity | |---|---| | Codeine phosphate | 0.3 g | | Lemon syrup | 20 ml | | Benzoic acid solution | 2 ml | | Chloroform spirit | 2 ml | | Compound tartrazine solution | 1 ml | | Purified water | 2 ml | | Syrup (q.s.) | 100 ml | Codeine phosphate is dissolved in water. To this, benzoic acid solution, chloroform spirit and compound tartrazine solution are added and mixed well. Then, lemon syrup is added and the volume is made up with syrup. ## Liquid dosage form used in oral cavity ### Sprays: Sprays may be defined as aqueous or oleaginous solutions in the form of coarse droplets or as finely divided solids to be applied topically, most usually to the nasopharyngeal tract or to the skin. Many commercial sprays are used intranasally to relieve nasal congestion and inflammation and to combat infection and contain antihistamines, sympathomimetic agents, and antibiotic substances. Because of the noninvasive nature and quickness with which nasal sprays can deliver medication systemically, in the future, several drugs that typically have been administered by other routes may be taken nasally. Most notably, insulin and glucagon may be administered in this fashion. It has been demonstrated that the administration of glucagon via a nasal spray can relieve hypoglycemic symptoms within 7 minutes, a definite advantage over conventional emergency intravenous glucose or intramuscular glucagon. * Other sprays that are employed against sunburn and heat burn contain local anesthetics, antiseptics, skin protectants, and antipruritics. * To break up a solution into small particles to be effectively sprayed or to facilitate the spraying of a powder, several mechanical devices are commonly employed: * **Plastic spray bottle:** gently squeezed to issue a spray of its contents. It is commonly used for nasal decongestant sprays as well as cosmetically, especially for body deodorant products. * **One-way pump sprays:** recently developed to deliver medication into the nose, are used for both prescription, e.g. Nasalide (Syntex), and nonprescription, e.g. Nostrilla (Boehringer Ingelheim), medicines. Their design will provide an advantage over the conventional sprays, which it prevents drawback contamination of nasal fluids into the bottle after administration, an advantage for someone trying to cope with viruses associated with the common cold. Atomizer with a rubber bulb at the end of the apparatus, which when squeezed causes a flow of air, some of which enters the glass reservoir and some of which exits from the opposite end of the system. The air forced into the reservoir causes the liquid to rise in a small dip tube, forcing the solution up and into the stream of air exiting the system. The air and the solution are forced through a jet opening and the liquid is broken up into a spray, the droplets being carried by the airstream. In other similar apparatus, the stream of air caused by the depression of the bulb does not enter the reservoir of solution but passes swiftly over it, creating a pressure change and sucking the liquid into the dip tube and into the airstream, in which it exits the system. ## Mouthwashes and gargles: Mouthwashes are aqueous solutions, often in concentrated form, containing one or more active ingredients and excipients. Mouthwash is used to enhance oral hygiene. It can be used therapeutically for reducing plaque, gingivitis, dental caries and stomatitis or cosmetically for reducing bad breath through the use of antimicrobial and flavoring agents. Flavors are used in conjunction with alcohol and humectants to overcome obnoxious odor and taste. Commonly employed flavoring agents are peppermint oil, spearmint oil, cinnamon oil, wintergreen oil, menthol and methyl salicylate. Mouthwashes have a pleasant taste and odor. In general, they are dispensed in white fluted bottles. The label should clearly indicate the proper directions for diluting the mouthwash before use, along with the auxiliary labeling, "For external use only" and "Not to be swallowed in large quantities." **Example: Compound sodium chloride mouthwash BPC** | Ingredient | Quantity | |---|---| | Sodium chloride | 15 g | | Sodium bicarbonate | 10 g | | Peppermint water (q.s.) | 1000 ml | Sodium bicarbonate and sodium chloride are dissolved in sufficient quantity of peppermint water. The volume is made up with the remaining peppermint water. * Other examples of mouthwashes are as follows: * Phenol and alkaline mouthwash * Potassium chlorate and phenol mouthwash * Thymol glycerin mouthwash * Hydrogen peroxide mouthwash * Buffered sodium perborate mouthwash ## Throat paints: Throat paints are viscous liquid preparations containing one or more medicaments and are used for throat and mouth infections. They are highly viscous due to their high content of glycerin. They are made viscous so that the drug would remain in contact with the mucus membrane for a longer time period. Throat paints are applied as such without dilution on the affected area with the help of a brush or cotton plug. They should be stored in coloured fluted airtight containers. The general requirements for labelling should be complied with. In addition, the containers should state “For external use only" and "Apply with brush." Throat paints are helpful in the treatment of pharyngitis, laryngitis and follicular tonsillitis. However, they suffer from the drawback of increased salivary secretion, due to which the patient may spit out the preparation. The formulation of throat paint requires viscous vehicles, flavouring agents, colouring agents and sweetening agents. Medicaments such as antiseptics, astringents and anti-infectives are commonly incorporated in throat paints. **Example: Mandl's paint** | Ingredient | Quantity | |---|---| | Iodine | 1.25 g | | Potassium iodide | 2.5 g | | Purified water | 2.5 m | | Peppermint oil | 10.42 ml | | Alcohol (95%) | 3.75 ml | | Glycerin (q.s.) | 100 ml | In this preparation, iodine acts as an antiseptic and potassium iodide dissolves the iodine. Peppermint oil acts as the flavoring agent and produces a cooling effect. Alcohol is used as a solubilizing agent for the peppermint oil. As the preparation contains iodine, it should be prepared in a glass apparatus. * Potassium iodide and iodine are dissolved in purified water using a glass mortar and pestle with a small portion of glycerin. To this, peppermint oil dissolved in alcohol is added and mixed and then sufficient glycerin is added to produce the required volume. * Other examples of paints are brilliant green and crystal violet paint, coal tar paint and tannic acid glycerin paint. ## Liquid dosage form istalled into body cavity ### Eye Drops: These are small-volume sterile aqueous or oily solutions or suspensions that are used for instillation on to the eyeball or within the conjunctival sac for a local effect. Eye drops solution should have the following essential characteristics: 1. It should be sterile. 2. It should be iso-osmotic with lachrymal secretions. 3. It should have neutral pH. 4. It should be free from foreign particles. 5. It should remain stable during its storage. Preparation of eye drops consists of the following four stages: 1. Preparation of bactericidal and fungicidal vehicles 2. Solution of the medicaments or active ingredients and if needed the appropriate adjuvants 3. Clarification 4. Sterilization * The preservative is dissolved in purified water in the prescribed concentration. All the medicaments and adjuvants are dissolved in the antimicrobial solutions to form a stable mixture. The solution is clarified by passing through a membrane filter having pore size of 0.2 mm to remove any particulate matter. The clarified solution is immediately transferred into final containers and sealed. Eye drops are sterilized by any one of the sterilization methods such as autoclaving, heating at 98°C-100°C for 30 minutes or filtration through 0.22 mm membrane filter. * Eye drops are dispensed in neutral glass containers. Either a glass dropper or plastic cap-nozzle is used for administration. Eye drops should be labelled "For external use only" along with the storage conditions to maintain its activity during storage. **Example: Sodium chloride eye lotion BPC** | Ingredient | Quantity | |---|---| | Sodium chloride | 9g | | Purified water (q.s.) | 1000 ml | This is a simple solution prepared by dissolving sodium chloride in purified water, filtered and sterilized. This is also called a normal saline solution. ### Ear Drops: Also known as otic or aural products, these are simple solutions of drugs in either water, glycerol, propylene glycol or alcohol/water mixtures for local use, and include antibiotics, antiseptics, cleansing solutions and wax softeners. They are applied to the external auditory canal as drops, sprays or washes. * These are solutions that are instilled into the ear with a dropper. Ear drops are generally use for cleaning the ear, softening the wax and treating mild infections. However, this may caus inconvenience to patients because they have to lie down or tilt their head at angle of 45° when ear drops are administered. The important consideration in the formulation of ear drops is the selection of vehicle. The vehicle should mix easily with ear wax and should make maximum contact between the drug and the tissues of the ear. Anhydrous glycerin and propylene glycols are the commonly used vehicles. * These vehicles remove the moisture from the tissue, thereby reducing the growth of microorganisms and inflammation. For the purpose of preservation, preservatives such as chlorobutanol and thiomersal are employed in the formulation. **Example: Sodium bicarbonate ear drops BP** | Ingredient | Quantity | |---|---| | Sodium bicarbonate | 5 g | | Glycerin | 30 ml | | Purified water (q.s.) | 100 ml | Sodium bicarbonate is dissolved in water. To this, glycerin is added and mixed well. Glycerin provides the softening capacity to the solution, and it reduces itching due to its emollient property. To this solution, the remaining quantity of water is added, and the required volume is made up. ### Nasal Drops: These are formulated as small-volume solutions in an aqueous vehicle that are instilled into the nose with a dropper. Nasal drops should be isotonic with nasal secretions using sodium chloride, having neutral pH and viscosity similar to nasal secretions. Because the buffering capacity of nasal mucus is low, formulation at a pH of 6.8 is necessary. Use of oily vehicle is restricted, because it inhibits the movement of cilia in the nasal mucosa and if used for long periods, it reaches the lungs and causes lipoidal pneumonia. Nasal drops are dispensed in colored fluted bottles fitted with a dropper or in a suitable plastic container. The label should bear the indication “For external use only." The drops are used to reduce the swelling of nasal mucosa and the underlying tissues. They reduce nasal congestion by retaining the solution within the nasal cavity. * Active agents for administration by this route for local use include antibiotics, anti-inflammatories and decongestants. The nasal route is also of major importance for specific types of drugs. * Formulation of nasal drops requires vehicles such as purified water and liquid paraffin, tonicity-adjusting materials such as sodium chloride and dextrose, preservatives such as chlorobutanol and benzalkonium chloride and buffers such as phosphate buffer. **Example: Ephedrine nasal drops BPC** | Ingredient | Quantity | |---|---| | Ephedrine hydrochloride | 9.14 g | | Chlorobutanol | 4.5 g | | Sodium chloride | 4.5 g | | Purified water (q.s.) | 1000 ml | Chlorobutanol is dissolved in a sufficient quantity of purified water. Ephedrine hydrochloride and sodium chloride are dissolved in purified water in a separate container. These two solutions are mixed together, and the final volume is adjusted with purified water to make up the required volume. ## Douches: A douche is an aqueous solution that is administered against a part or into a cavity of the body. It acts as a cleansing agent or antiseptic. Douches are directed to the appropriate body parts by usin bulb syringe. They are more frequently dispensed in the form of powder with directions for dissolving in a specified quantity of warm water. Compound sodium borate solution National formulary is used as nasal or pharyngeal douch. Douches can be used to clean the body cavities and to promote healing of wounds. * Medicaments commonly employed as douches include: 1. Cleansing agents, for example, sodium chloride and sodium bicarbonate; 2. Antiseptics, for example, chlorhexidine and lactic acid; and 3. Astringents, for example, tannic acid and zinc sulfate. * Douches are classified into the following four types: 1. Eye douche-used to remove foriegn particles and discharges from the eyes, is applied gently at an oblique angle and is allowed to run from the inner to outer corner of the eye 2. Pharyngeal douche-used to prepare the interior of the throat for an operation and to cleanse it in conditions of formation of discharge of pus. 3. Nasal douche-used to cleanse nasal passage 4. Vaginal douche-used for irrigation cleansing of the vagina and should be sterile in nature. ## Vaginal Douches: Solutions may be prepared from powders, liquid solutions or liquid concentrates. In using liquid concentrates, the patient is instructed to add the prescribed amount of concentrate (usually a teaspoonful or capful) to a certain amount of warm water (frequently a quart). The resultant solution contains the appropriate amount of chemical agents in proper strength. The agents are similar to the ones described for douche powders. Powders are used to prepare solutions for vaginal douche, i.e., for irrigation cleansing of the vagina. **Example: Potassium permanganate vaginal douche** | Ingredient | Quantity | |---|---| | Potassium permanganate | 1.0 g | | Purified water (q.s.) | 1000 ml | Potassium permanganate is soluble in water. Potassium permanganate is triturated with appreciable amount of purified water in a pestle and mortar. Trituration is continued until potassium permanganate gets dissolved completely in water. The solution is filtered through sintered glass filter. To this, purified water is added to make up the volume and is packed in a suitable container. The user simply adds the prescribed amount of powder to the appropriate volume of warm water and stirs until dissolved. Among the components of douche powders are the following: 1- Boric acid or sodium borate 2- Astringents, for example, potassium, alum, ammonium alum, zinc sulfate 3- Antimicrobials, for example, oxyquinoline sulfate, povidone iodine 4- Quaternary ammonium compounds, for example, benzethonium chloride 5- Detergents, for example, sodium lauryl sulfate 6- Oxidizing agents, for example, sodium perborate 7- Salts, for example, sodium citrate, sodium chloride 8- Aromatics, for example, menthol, thymol, eucalyptol, methyl salicylate, phenol Douche powders are used for their hygienic effects. A few douche powders containing specific therapeutic anti – infective agents such as those used against monilial and trichomonal infections. ## ENEMAS: Aqueous or oily solutions, as well as emulsions and suspensions, are available for the rectal administration of medicaments for cleansing, diagnostic or therapeutic reasons, and are termed enemas. * Enemas are solutions intended for introduction into the rectum or colon to cause evacuation of bowel or to bring about local or systemic effects. They are used for diagnostic purpose, especially for X-ray examination of bowel. Enemas are classified into the following five types: 1. Cleansing or evacuating enema, for example, saline solution 2. Carminative enema, for example, milk, olive oil 3. Retention enema, for example, paraldehyde, starch and water 4. Lubricating enema, for example, vegetable and mineral oil 5. Medicated enema, for example, sodium phosphate, decussate sodium * Administration of enemas requires the help of trained personnel, a pharmacist or a nurse. Enemas are introduced after warming the solution to body temperature. The volume of enema administered is based on the age and condition of the patient. * Enemas are dispensed usually in volume of 1000 ml in colored fluted glass bottles, which should bear the labels “For external use only," "Lubricate the nozzle before administration," and "Warm the solution to body temperature,” “For external use". They are suitable for drugs that cannot be given through oral or parenteral route. However, enemas may cause discomfort to the patients. Moreover, the liquid pressure should be controlled, as high pressure may cause pain and rupture the intestinal wall. Formulation of enema requires suitable soluble drugs in the selected solvent and stabilizers. Since the drugs used are mostly water soluble, simple solution method is usually employed for manufacture. Commonly used medicaments include laxatives, sedatives and anthelmintics. ## 1- Retention Enemas: A number of solutions are administered rectally for local effects (e.g., hydrocortisone) or for systemic absorption (e.g., aminophylline). In the case of aminophylline, rectal administration minimizes the undesirable gastrointestinal reactions associated with oral therapy. Clinically effective blood levels of the agents are usually obtained within 30 minutes following rectal instillation. Corticosteroids are administered as retention enemas or continuous drip as adjunctive treatment of some patients with ulcerative colitis. ## 2- Evacuation Enemas: Are rectal enemas that used to cleanse the bowel. Commercially, they are available in disposable plastic squeeze bottles containing a premeasured amount of enema solution, e.g. sodium phosphate and sodium biphosphate, glycerin and docusate potassium, and light mineral oil. The pharmacist should advise the patient to gently insert the tip of the product with steady pressure, not necessary to squeeze all of the contents out of the bottle and the product will work within 5 to 10 minutes. * **Example: Glycerin enema** * Glycerin - 50 ml * Purified water - 100 ml As glycerin is miscible with water, it gets mixed well and forms a homogeneous solution. Glycerin stimulates the rectal mucosa, promotes defecation and lubricates and softens fecal material. ## Intermediate products There are many pharmaceutical solutions that are designed for use during the manufacture of other preparations and which are rarely administered themselves. ### Aromatic Water: Are clear, aqueous solutions saturated with volatile oils, aromatic or volatile substances. They are no longer in widespread use and in the past, aromatic waters were prepared from a number of volatile substances, e.g. orange flower oil, peppermint oil, rose oil, anise oil, spearmint oil, wintergreen oil, camphor, and chloroform. Naturally, the odors and tastes of aromatic waters are of the volatile substances from which they are prepared. Most of the aromatic substances have very low water solubility, and even though the water may be saturated, its concentration of aromatic material is still rather small. Aromatic waters may be used for perfuming and / or flavoring. They are usually manufactured as concentrated waters and are then diluted, traditionally 1:40 in the final preparation. ### Spirits: *Are alcoholic or hydroalcoholic solutions of volatile substances. Generally, the alcoholic concentration of spirits is rather high, usually > 60 %. Because of the greater solubility of aromatic or volatile substances in alcohol than in water, spirits can contain a greater concentration of these materials than the corresponding aromatic waters. When mixed with water or with an aqueous preparation, the volatile substances present in spirits generally separate from the solution and form a milky preparation. They are used pharmaceutically as flavoring agents and medicinally for the therapeutic value of the aromatic solute. For medicinal purposes, spirits may be taken orally, applied externally, or used by inhalation. When taken orally, they are generally mixed with a portion of water to reduce the pungency of the spirit. Depending on materials, spirits may be prepared by simple solution, solution by maceration, or distillation. The spirits most recently official in the USP – NF are aromatic ammonia spirit, camphor spirit, compound orange spirit, and peppermint spirit. ### Dilute Acids: Are aqueous solutions prepared by diluting the corresponding concentrated acids with purified water. The strength of a diluted acid is expressed on a % w/v basis, whereas the strength of a concentrated acid is expressed on a % w / w basis. * Concentrated HCl contains > 35 gm < 38 gm solute (i.e. absolute HCl) per 100 gm of acid and is therefore 36.5% w/w average in strength. Diluted HCl contains 9.5 gm - 10.5 gm of solute per 100 mL of solution and is therefore 10 % w / v average in strength. If one wished to prepare 100 mL of the diluted acid from the concentrated acid, one would require 10 gm of solute. * $$ \frac{36.5 \text{ (solute)}}{100 \text{ gm (conc.acid)}} = \frac{10\text{ gm (solute)}}{x \text{ (gm conc.acid)}} $$ Solving for x: $$ 36.5x = 1,000 \text{ gm} $$ $$ x = 27.39 \text{ gm (conc. acid)} $$ Thus, 27.39 gm of concentrated acid is required to supply 10 gm of solute needed for the preparation of 100 mL of the diluted acid. * One step further to determine the volume of concentrated acid that corresponds to the calculated weight using the concentrated acid's specific gravity, define as the ratio, expressed decimally, of the weight of a substance to the weight of an equal volume of a standard, both substances having the same temperature, and water is an excellent choice for a standard. * At 4°C, the density of water is 1 gm per cubic centimeter. Because the USP states that 1 mL may be considered the equivalent of 1 cc, in pharmacy, water is assumed to weigh 1 gm per milliliter. By the following equation used to calculate specific gravity, a substance having a density the same as water would have a specific gravity of 1.0: * $$ Sp. Gr. = \frac{\text{weight of substance}}{\text{weight of an equal volume of water}} $$ * Concentrated HCl has a specific gravity of 1.17, then the volume of 27.39 gm concentrated HCl calculated as follows: $$ \text{weight of conc. acid equal of water} = \frac{\text{weight of conc.acid}}{\text{Sp. Gr. of conc.acid}} $$ * Thus, because 23.41 gm of water measures 23.41 mL and it is equal in volume to the concentrated HCl, the latter also measures 23.41 mL, and this is the amount required to prepare 100 mL of the 10% w/v diluted HCl. * The following simplified formula can be used to calculate the amount of a concentrated HCl required in the preparation of a specific volume of the corresponding diluted HCl : $$ \frac{\text{percentage strength of diluted acid X volume of diluted acid to be prepared}}{\text{percentage strength of concentrated acid X specific gravity of concentrated acid}} = \text{volume of concentrated acid to use} $$ * Recalculating the preparation of 100 mL of diluted hydrochloric acid from the concentrated acid gives the following: $$ \frac{10 X 100}{36.5 X 1.17} = 23.41 \text{ ml of concentrated acid to use} $$ There is very little use of diluted acids in medicine today. Because of its antibacterial effects, acetic acid finds application as a 1% solution in surgical dressings, 0.25 % bladder irrigating solution, and as a spermatocidal in some contraceptive preparations. ## Extraction Methods for Preparing Solutions: - *Introduction: *Certain pharmaceutical preparations are prepared by extraction, i.e., by withdrawal of desired constituents from crude drugs through the use of selected solvents in which the desired constituents are soluble. Crude drugs are vegetable or animal drugs that have undergone no other processes than collection, cleaning, and drying. *The solvent systems used in extraction are selected on the basis of their capacity to dissolve the maximum amount of desired active constituents and the minimum amount of undesired constituents. The active constituents of a plant drug are of the same general chemical type, similar solubility characteristics, and can be simultaneously extracted with a single solvent or a single solvent mixture. In drug extraction, the solvent or solvent mixture is referred to as the menstruum, and the plant residue, which is exhausted of active constituents, is termed the marc. *The selection of the menstruum to use in the extraction of a crude drug is based primarily on its ability to dissolve the active constituents: - 1- Because of its ready availability, cheapness, and good solvent action for many plant constituents, water has some use in drug extraction, particularly in combination with other solvents. However, as a sole solvent, it has many disadvantages: * Most active plant constituents are complex organic chemical compounds that are less soluble in water than in alcohol, * Water has a great solvent action on such plant constituents as sugars, gums, starches, coloring principles, and tannins, most of these are not particularly desirable components of an extracted preparation, * Water also tends to extract plant principles that separate upon standing in the extractive, leaving an undesired residue, and * Unless preserved, aqueous preparations serve as an excellent growth media for molds, yeasts, and bacteria. When water alone is employed as the menstruum, alcohol is frequently added to the extractive or to the final preparation as an antimicrobial preservative. 2- Hydroalcoholic mixtures are the most versatile and the most widely employed menstrua. They combine the solvent effects of both water and alcohol, and the complete miscibility of these two agents permits flexible combining of the two agents to form solvent mixtures most suited to the extraction of the active principles from a particular drug. A hydroalcoholic menstruum generally provides inherent protection against microbial contamination and helps to prevent the separation of extracted material on standing. 3- Glycerin, a good solvent for many plant substances, is occasionally employed as a cosolvent with water or alcoholic menstrua because of its ability to extract and then prevent inert materials from precipitating upon standing. It is especially useful in this regard in preventing separation of tannin and tannin oxidation products in extractives. Because glycerin has preservative action, depending on its concentration in the final product, it may contribute to the stability of a pharmaceutical extractive. ## Methods of Extraction: The principal methods of drug extraction are maceration and percolation. Generally, the method of extraction selected for a given drug depends on several factors, including: 1| the nature of the crude drug, 2| its adaptability to each of the various extraction methods, and 3| the interest in obtaining complete or nearly complete extraction of the drug. Frequently, a combination of maceration and percolation is actually employed in the extraction of a crude drug. The drug is macerated first to soften the plant tissues and to dissolve much of the active constituents, and percolation separates the extractive from the marc. ### Maceration: [Latin macerate, meaning to soak] A process in which the properly comminuted drug is permitted to soak in the menstruum until the cellular structure is softened and penetrated by the menstruum and the soluble constituents are dissolved. Two options: - * The drug to be extracted is generally placed in a wide-mouth container with the prescribed menstruum, the vessel is stoppered tightly, and the contents are agitated repeatedly over a period usually ranging from 2 to 14 days. The agitation permits the repeated flow of fresh solvent over the entire surface area of the comminuted drug. * Place the drug in a porous cloth bag that is tied and suspended in the upper portion of the menstruum, much the same as a tea bag suspended in water to make a cup of tea. As the soluble constituents dissolve in the menstruum, they tend to settle to the bottom because of an increase in the specific gravity of the liquid due to its added weight. Occasional dipping of the drug bag may facilitate the speed of the extraction. * The extractive is separated from the marc by expressing the bag of drug and washing it with additional fresh menstruum, the washings being added to the extractive. If the maceration is performed with the drug loose, the marc may be removed by straining and / or filtration, with the marc being washed free of extractive by the additional passage of menstruum through the strainer or filter into the total extractive. For drugs containing little or no cellular material, e.g. aloe, and tolu, which dissolve almost completely in the menstruum, maceration is the most efficient method of extraction. Maceration is usually conducted at a temperature of 15 °C – 20 °C for 3 days or until the soluble matter is dissolved. ### Percolation: [Latin per, meaning through, and colare, meaning to strain] * A process in which a comminuted drug is extracted of its soluble constituents by the slow passage of a suitable solvent through a column of the drug. The drug is packed in a special extraction apparatus termed a percolator, with the collected extractive called the percolate. * In the process of percolation, the flow of the menstruum over the drug column is generally downward to the exit orifice, drawn by the force of gravity as well as the weight of the column of liquid. In certain specialized and more sophisticated percolation apparatus, additional pressure on the column is exerted with positive air pressure at the inlet and suction at the outlet or exit. The shapes of percolators in common laboratory and small – scale use are: - * The cylindrical percolator is particularly suited to the complete extraction of drugs with a minimal expenditure of menstruum. By the passage of the menstruum over the drug contained in a high, narrow column (rather than in a lower, wider column), each drug particle is more repeatedly exposed to the passing solvent. * A funnel shaped percolator is useful for drugs that swell a great deal during maceration, because the large upper surface permits expansion of the drug column with little risk of a too tightly packed column or breakage of a glass percolator. ## Example Preparations Prepared by Extraction Processes: ### Fluidextracts: *Are liquid preparations of vegetable drugs prepared by percolation. They contain alcohol as a solvent, preservative, or both and are made so that each milliliter contains the therapeutic constituents of 1 gm of the standard drug that it represents. *Because of their concentrated nature, many fluidextracts are considered too potent to be safely self-administered, and their use per se is almost nonexistent in medical practice. *Also, many fluidextracts are simply too bitter-tasting or otherwise unpalatable to be accepted by the patient. Therefore, most fluidextracts today are either modified by the addition of flavoring or sweetening agents before use or used as the drug source of other liquid dosage forms, such as syrups. ### Extracts: *Are concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents of the respective drugs with suitable menstrua, evaporation of all or nearly all of the solvent, and adjustment of the residual masses or powders to the prescribed standards. Extracts are potent preparations, usually between two and six times as potent on a weight basis as the crude drug. •In the manufacture of most extracts, percolation is employed to remove the active constituents from the drug, with the percolates generally being reduced in volume by distillation under reduced pressure to reduce the degree of heat and to protect the drug substances against thermal decomposition. The extent of removal of the solvent determines the final physical character of the extract. *Extracts are made in three forms: (a) semiliquid extracts or those of a syrupy consistency prepared without the intent of removing all or even most of the menstruum, (b) pilular or solid extracts of a plastic consistency prepared with nearly all of the menstruum removed, and (c) powdered extracts prepared to be dry by the removal of all of the menstruum insofar as is feasible or practical. *Pilular and powdered extracts differ only by the slight amount of remaining solvent in the former preparation, but each has its pharmaceutical advantage because of its physical form. For instance, the pilular extract is preferred in compounding a plastic dosage form such as an ointment or paste or one in which a pliable material facilitates compounding, whereas the powdered form is preferred in the compounding of such dosage forms as powders, capsules, and tablets. ## Resins and oleoresins: *Resins are amorphous (having no definite shape, for or structure) products of complex chemical nature. These are amorphous mixtures of essential oils, oxygenated products of terpene and carboxylic acids found as exudation from the trunk of various trees. *Natural resins are solid or semisolid exudations from plants or from insects that feed on plants. Chemically these exudations are the oxidized terpenes of the volatile oils of plants. ### Properties of Resins: - * They are transparent or translucent acids, semi acids or liquid substances containing a large number of carbon atoms. Most of the resins are heavier than water. * They are insoluble in water but soluble in alcohol, volatile oils, fixed oils, chloral hydrate and non-polar organic solvents like benzene or ether. * They are hard, electrically non-conductive and combustible masses. When heated, they soften and ultimately melt. * They are usually formed in schizogenous or schizolysigenous cavities or ducts as end products of metabolism. * Chemically, they contain organic acids, alcohols, esters, and neutral resins. * Pharmaceutical resins are obtained from plants and animals by one of the following methods: - * By extraction with alcohol and precipitation with water e.g.: -jalap, podophyllum, ipomoea etc. * By distillation for separation of oil eg:- copaiba, colophony etc. ### Example of Resins : 1. **Podophyllum, Resin, USP;** is obtained by percolating dried rhizome and Podophyllum Peltatum roots. Prepared as a dispersion in alcohol in compound Benzoin Tincture, USP; it is used as a topical caustic for the treatment of certain papillomas. 2. **Example of natural resin obtained as exudation Colophony Resin.** Rosin, NF, is a solid resin which remains after the distillation of turpentine. It has many traditional uses; pharmaceutically, it is widely used as an adhesive. ### Oleoresines * Oleoresins are homogeneous mixtures of resins and volatile oils. Depending on the relative amount of volatile oil in the mixture, oleoresins may be liquid, semisolid, or solid. It's either natural or synthetic. * Naturally extracted from the trunk of trees that contain e.g. turpentine. * Synthetic oleoresin e.g. ginger oleoresin, is prepared by extracting oleoresin from ginger as coarse powder by percolation with a suitable solvent (alcohol, ether, acetone) ### Glycerits * It is not extract fluid, or product. * It is preparation that contains not less 50% by weight of glycerin and medicinally agent. * It is very viscose either used such as or diluted in other preparation. Some times it is called glycerines. **Examples** 1. glycerin otic solution contain phenazon and benzocaine (local ansethic) in glycerol. Used as ear drop. It should be stored in air tight container and protected from light. 2. phenol glycerin (BP) contains * Phenol - 160 gm * Glycerin - 84 gm * If 40 ml of it is diluted to 100ml with glycerin we will get what we called phenol ear drop. * Phenol ear drops should not be diluted with water because phenol crystals will precipitate in otic tissue and form caustics in otic preparation. * The benefit of glycerin in otic preparation; 1. Preservative 2. Increase the viscosity to prolong the contact of active substance to the infected area 3. Dissolving the insoluble substance 4. Reduce pain, swelling, and oedema. ## colloidal Dispersions