Solutions

•Definitions

•A Solution is a homogeneous mixture of two or more substances
                            OR

•A solution is a homogeneous mixture of solute and solvent      
                   

                           OR

A solution is a homogeneous mixture of two substances but consisting of one phase.
•Homogeneity: something evenly distributed

•Heterogeneity: something not distributed evenly in space; a clump or cluster.

•A Solute is dissolved in a Solvent.

–solute is the substance being dissolved

–solvent is the liquid in which the solute is dissolved–an aqueous solution has water as solvent

•Binary solution: A homogeneous mixture consisting of one phase and containing only two components i.e. one solute and one solvent e.g. Solution of NaCl in water.

•Dilute Solutions:
 A solution containing relatively small quantity of solute as compared with the amount of solvent.

•Concentrated Solution: A solution containing large amount of solute in the solution than that in dilute solution.

•Un-saturated solution: a solution in which more solute can be dissolved at a given temperature is called as an unsaturated solution.
•A Saturated solution is one where the concentration is at a maximum - no more solute is able to dissolve at a given temperature.

–A saturated solution represents an equilibrium: the rate of dissolving is equal to the rate of crystallization.  The salt continues to dissolve, but crystallizes at the same rate or under these condition the number of molecules leaving the solute is equal to the number of molecule returning to the solid phase i.e. solute.

•Types of Solutions: Based on physical states of solute and solvent:

•      BASED ON PARTICLE SIZE:•Solution systems or dispersed systems are those system in which one substance ( i.e. solute) is dispersed through an other phase ( i.e. solvent) called continuous phase. So the solute is called dispersed phase or dispersoid and solvent as solvent as continuous phase
•Solutions may be categorized on the basis of dispersion as follows:

•Ultra filtration is a separation process using membranes with a pore sizes in the range of 0.1 to 0.001 micron. Typically, ultra filtration will remove high molecular weight substances, colloidal materials and organic polymeric molecules. Low molecular weight organics and ions such as sodium, calcium, magnesium and sulfates are not removed.

Vitamins

·        Fat soluble Vitamins

ü  Vitamin A (Retinol)

ü  Vitamin D (Calciferol)

ü  Vitamin E (Tocopherol)

ü  Vitamin K

·        Water soluble Vitamin

ü  Vitamin C (Ascorbic acid)

ü  Niacin

ü  Biotin

ü  Folic acid

ü  pantothenic acid

ü  Lipoic acid

ü  Vitamin B complex group molecules

§  Vitamin B₁(Thiamin)

§  Vitamin B₂(Riboflavin)

§  Vitamin B₃(Pyridoxin)

§  Vitamin B₄(Cyanocobalamine)

·        

Comparison of two major types of vitamin

Properties	Fat soluble vitamins	Water soluble vitamins
Soluble in fat	Soluble	insoluble
Soluble in water	Insoluble	soluble
Absorption	Along lipids require bile salts	Absorption is simple
Carrier proteins	Present	No carrier protein is present
Storage	Stored in liver	No appreciable storage
Excretion	Not excreted	Excreted
Deficiency	Manifests only when stores are depleted	Manifests rapidly as no storage
Treatment of deficiency	Single large doses may present deficiency	Regular dietary supplements are required
Major vitamins	A,D,E & K	B & C

Vitamin A

Chemistry:

Compounds of vitamin A activity referred to as pterinoids. They are poly isoprenopid compounds with beta-ionone ring or trimethylcyclohexenyl ring compounds.

Precursors of provitamin of vitamin A beta-carotene give rise to two beta-ionone rings connected by poly prenoid or hydrocarbon chain.

Dietary Sources:

Food of animal origin is retinyl esters.

Among Diary sources i.e. butter, milk & cheese. Highest concentration is present in the liver oils of certain species of fish e.g. shark, cod etc. Livers of fresh water fish contains Vitamin A₂

It is also found in deep green, yellow orange fruits & vegetables e.g. carrots and broocoli, kale, pumpkins, sweet potatoes, peach, apricots etc. Recently “spirulina” species of algae are found to be good sources.

Properties:

All yellow crystals of Vitamin A are almost odorless or fish like odor. They have melting point of about 63C⁰ to 64C⁰.They are soluble in alcohol, fixed oils, organic solvents i.e. ether, chloroform etc.

They are stored in air tight containers protected from light. They are made stable by the use of antioxidants from light and oxygen.

Daily requirement:

§  Children……….400 to 600 mg/day

§  Men……………..750 to 1000 mg/day

§  Women……….750 mg/day

Hypervitaminosis:

It is characterized by failure, irritability, anorexia, and loss of weight, vomiting & other GIT disorders. Fever, skin changes, alopecia dry hairs, cracking and bleeding of lips, anemia, headache, pain in bones and joints.

Deficiency:

The major problems areNight blindness, Xerothalmia&keratomalaria.

1.       Small triangular patches on the inner outside of cornea covered by a material like formed termed as bitots spots.

2.       When xerothalmia persists for a drug for a long period of time it progresses to keratomalaria  (softening of cornea) so it becomes dry, rough and scaly.

3.       Retardation of growth accompanied by defects of skull bones on CNS may produce nerve degeneration and paralysis.

4.       Its suitable quantity is required for normal activity of mitochondria and deficiency interferes with oxidative phosphorylation.

Vitamin K

It is also known as Antihaemorragicfactor.It has basically two types;

1.       Vitamin K₁ (mainly obtained from Alfalfa leaves)

2.       Vitamin K₂ (mainly obtained from fish meals and intutinal bacterial flora)

Chemistry:

These are derivatives of phytal chains. First two are natural while other two are synthetic types of Vitamin K.

1.       Vitamin K₁ (Phyeloquinone)

2.       Vitamin K₂ (Farnoquinone)

3.       Vitamin K₃ (Manadione)

4.       Vitamin K₄ (Menadial)

Sources:

It is mainly obtained from green fresh leafy vegetables e.g. Alfalfa, cauliflower, cabbage, tomatoes, soya beans etc.

An intestinal microorganism possesses high Antihaemorragic concentration which may be 11 to 38 times as active as alfalfa. The names of the microorganisms are Bacillus cereus, Bacillus subtilis, Bacillus mycoids, Bacteriaumproteus, mycobacterium tuberculosis, Sarcinalutea and Staphylococcus aureus etc.

Daily requirement:

50 to 100 mg/day should be available in normal diet.

Deficiency:

Prolong use of broad spectrum antibodies and sulfa drugs lead to fall of prothrombin level in plasma an abnormal long coagulations times and tendency to spontaneous haemorrage.

Functions:

1.       It is very important to maintain adequate plasma level of the protein prothrombin (factor ӏӏ) and three other essential clotting factors i.e. proconvertin (factor VII), autoprothrombin (factor IX) andstuart power factor (factor X).

2.       During clotting the circulating thrombin i.e. required for the production of thrombin which converts fbrin into fibrinogen.

3.       It is involved in the production of two anticoagulant proteins as proteins C & S.

4.       It is administerded with bile in pre-operative and post-operative jaundiced patients to main tain normal protein levelk in blood.

5.       It is necessary cofactor in oxidative phosphorylation being associated with mitochondrial lipids. The normal process of oxidative process of phosphorylation is released when vitamin K is added to them.

Hypervitaminosis:

Administration of large quantities of medicine may result in toxicity as hemolysis, hyperbilirubinemia and brain damage.

Vitamin E

Chemistry:

It was discovered in 1936. It is also known as antisterility factor or tocopherol. It is greenish yellow odorless, viscous, oily liquid, free soluble in organic solvents and fixed oils.

Different degrees of antisterility factors;

§  Processes antioxidant purposes

§  Include a group of 8 compounds

§  Among these α, β, γ and δ are important.

Basic structure of tocopherol shows that;

§  Chromane ring i.e. tocol

§  Trimethyltridecyl i.e. saturated hydrocarbon side chain)

Methyl substituted tocol derivatives;

1.       α-tocopherol  (5,7,8-trimethyl tocol)

2.       β-tocopherol  (5,8-dimethyl tocol)

3.       γ-tocopherol  (7,8-dimethyl tocol)

4.       δ-tocopherol  (8-methyl tocol)

Sources:

Tocopherols are abundant in wheat germs, rice germs, corn germs, lettuce, soyas, cotton seed oil. There is an evidence that some green leafy vegetables and rose hips contains more vitamin E than wheat germ.

Biochemical role of Vitamin E:

1.       It is a powerful natural antioxidant.

2.       Free radicals are greatly generated in living systems products of oxidative detoriation of poly unsaturated fat would attack biomembranes, while vitamin E converts free radicals into non harmful form.

3.       Protects RBC’s from hemolysis by preventing the peroxidation. It keeps the structural and functional integrity of all cells.

4.       It shows down aging process which is due to cumulative effects of free radicals.

5.       It ppt’s in nucleic acid metabolism b/c of tocopherols are component of cytochrome reductase segment of terminal respiratory chain.

6.       It has a role in the regulation of protein synthesis.

7.       It has been investigated to have an effect on enzymes e.g. creatine kinase and liver Xanthine oxidase.

Requirement:

·         Males 10mg/day

·         Females 08mg/day

·         During pregnancy its requirement is about 10mg/day. While during lactation 12mg/day.

Deficiency:

Human deficiency has not been reported.

In volunteers the vitamin E deficiency produced increase fragility of RBC’s, muscular weakness and creatine urea.

Hypervitaminosis:

It is observed only in large doses in animal causes reversible symptoms as skeletal muscle weakness, GIT disorders and disturbances of reproductive functions.

Vitamin B₁

Chemistry:

It consists of Thiazole ring and pyridine ring. It is also called Thiamin.

Sources:

Ø  Richest sources include dried yeast (03 to 06 mg/100g)

Ø  Rice polishing (2 to 3 mg), wheat germ (1.5 to 2.5 mg)

Ø  Whole cereals (0.4 to 0.1 mg), while in leguminous oils, seed and meat (0.3 to 0.4 mg)

Requirement:

·         Total concentration of thiamin in the body of an adult is in the range of 20 to 25 mg.

·         Its daily requirement is 1 to 1.5 mg/day.

Physiological role of thiamin:

1.       The co-enzyme form is thiamin pyrophosphate (TPP) it is used in oxidative decarboxylation of alpha-ketoacids e.g. pyruvate carboxylase.

2.       A component of pyruvate dehydrogenase (an enzyme) that catalyze the breakdown of the pyruvate to acetyl CoA and CO₂.

3.       Biochemical reactions require TPP in the decarboxylation of alpha-ketoglutarates to succinyl CoA and CO₂.

4.       Second group of enzymes that use TPP as coenzyme as Transketolase in the Hexose monophosphate shunt pathway of glucose.

5.       The main role of carbohydrate metabolism so its requirement is increased along with higher intake of carbohydrate.

6.       In patients on parenteral nutrition who receive all their calories in the form of glucose than thiamin requirements are high.

Deficiency & Manifestations:

It results in severe Neuromuscular syndromes i.e. beriberi which may be classified into many types;

§  Dry beriberi

§  Wet beriberi

§  Acute beriberi

The signs and symptoms of clinical beriberi are loss of strength, fatigue, headache, dizziness, nervousness, loss of appetite, dyspepsia etc.

Deficiency:

Other forms of thiamin deficiency which are seen clinically are alcoholic poly neuritis with motar and sensory defects in chronic in alcoholics. Alcohol utilization needs large doses of thiamin. At the same time alcoholics take less nutritive food leading to deficiency.

Vitamin B₂

Chemistry:

It is also called Riboflavin. It is an orange yellow compound. Chemically it contains o-ribitol (ribose alcohol) attached to heterocyclic parent ring structure that is dimethyl isoallorazine or simply it is 7, 8-dimethyl-10-isoallorazine.

Dietary sources:

Rich sources are liver, dried yeast, egg, whole milk and milk powder. Good sources are fish, whole cereals and green leafy vegetables.

Requirement:

 A daily dietary intake of about 1.1 to 1.7 mg/day is required. Increased quantity is needed during pregnancy and lactation.

Toxicity:

It is not reported but large doses result in light yellow de-coloration of urin.

Functions:

1.       Riboflavin make two co-enzymes B₂ monophosphate usually called flavin mononucleotide and other is flavin dinucleotide.

2.       FMN is the co-enzyme of cytochrome C reductase, L-aminoacid dehydrogenase etc.

3.       FAD is the co-enzyme of Xanthine oxidase, liver, aldehyde oxidize and acyl CoA dehydrogenase.

4.       The formation of FMN and FAD is increased by the thyroid hormone and adrenal steroids. The enzyme containing riboflavin are called flavor protein, they carry out redox reactions.

Vitamin B₆

Chemistry:

Pyridoxine is one of the compounds that can be called vitamin B₆, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. Its hydrochloride salt pyridoxine hydrochloride is often used. They mostly exhibit vitamin activity inter-convertible in-vivo.

Source:

Vitamin B₆ is widely distributed in foods in both its free and bound forms. Good sources include meats, whole grain products, vegetables, nuts and bananas.

Requirement:

·         Males……….1.3 mg/day

·         Females……1.5 mg/day

Requirement is increased during pregnancy and lactation.

Functions:

·         The primary role of vitamin B₆ is to act as a coenzyme to many other enzymes in the body that are involved in metabolism. This role is performed by the active form, pyridoxal phosphate.

Vitamin B₆ is involved in the following metabolic processes:

                                                                i.      Amino acid, glucose and lipid metabolism

                                                              ii.      Neurotransmitter synthesis

                                                             iii.      Histamine synthesis

                                                            iv.      Hemoglobin synthesis and function

                                                              v.      Gene expression

·         It involves in the lipid metabolism as well.

·         It also causes Gluconeogenesis.

Deficiency:

The classic clinical syndrome for B₆ deficiency is a seborrhoeic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms ofsomnolence, confusion, and neuropathy.

Toxicity:

Adverse effects have only been documented from vitamin B₆ supplements and never from food sources.

Powders

Powders

Powders are solid dosage form of medicaments which are made for internal and external purposes. They are available in amorphous and crystalline form. Drugs are prepared in different forms and shapes but many of them are prepared by using powder in one way or the other incompatibility (the quality of being discordant).

Advantages and disadvantages of powder:

The various merits and demerits of powders are discussed below;

Advantages:

1.       Many of drugs are available in powder form it become convenient for physician to prescribe specific amount of medicaments.

2.       Powders are less in compatible than liquids. Large quantities of bulky drugs which are difficult to administer can be easily taken with the help of liquid.

3.       They are easier to carry than liquids.

4.       They are more stable than liquids.

5.       Chemical reactions take place more easily in liquids than powders in atmospheric condition.

6.       Small particles of powders produce more rapid dissolution in body fluids than other dosage form.

7.       They are more economical for extemporaneous preparations.

8.       They are convenient for pediatric (child) and geriatric patients (old aged people).

Disadvantages:

1.       Drugs which deteriorate on exposure to atmospheric conditions are not suitable for powders.

2.       Bitter, nauseous, corrosive and unpalatable drugs can’t be dispensed in powder form.

3.       Deliquescent and hygroscopic drugs can’t be dispensed in powder form because they absorb moisture.

4.       Volatile drugs are not suitable for powder form because they lose their efficacy.

Classification of Powders

·         Simple and compound powders for internal use.

·         Granular and effervescent powders for internal use.

·         Bulk powders for external use.

·         Dusting powders, insufflations (used to insert into different body cavities) and tooth powders.

Practice size analysis:

Before the use of powders and other solid materials in pharmaceutical products characterized to determine their physical and chemical properties. It includes morphology, purity, solubility, stability, particle size and impurity.

The particles of pharmaceutical powders may be range from extremely coarse about 10mm in diameter to extremely fine approaching to colloidal dimension of micron or less. To characterized the particle size in USP;

Ø  Very coarse:Powders of vegetable and animal drugs are officially defined as very coarse. All particles pass through the 8 sieve and not more than 20% through a no. 50 sieve

Ø  Coarse:All particles pass through a number 20 sieve and not more than 40% through sieve number 60.

Ø  Moderately coarse:All particles pass through a number 40 sieve and not more than 40% through sieve number 80.

Ø  Fine: All particles pass through a number 60 sieve and not more than 40% through sieve number 100.

Ø  Very fine:All particles pass through a number 80 sieve, there is no limit to to greater fineness.

Blending powers:

These are formed when two or more than two powdered substances are to be combined to form a uniform mixture. It is best to reduce the particle size of each powder before weighing and blending.Depending upon the nature of ingredients amount of powders and equipment, powders may be blended by;

Ø  Spatulation:it involves the using spatula on white papers or slides to decrease the particle size.

Ø  Trituration:It includes the reduction of particle size on small scale by using pestle and mortar i.e. levigation& pulverization.

Ø  Sifting:For sifting process we require sifters i.e. any containers in which two substances are used. It is not used for the substances which produce therapeutic effects in small quantity i.e. potent drugs. In involves the usage of different types of machines for example; V-type, M-type and ribbon type machines.

Ø  Tumbling:Another method of powder mixture is tumbling. In this process powder is mixed in closed chamber by using motorized chamber for example H-type, Ribbon type or U-mixture. H-type total capacity is calculated. The 30% of the volume of total substance is reduced.

Ø Medicated powders:

Some medicated powders are intended to be used internally and externally. Some powders are taken internally with the help of water. Some powders are inhaled for local or systemic purposes; other dry powders are commercially packaged for constitution with liquid solvent and vehicle. Some used for parenteral and others are used as vaginal douches.

Ø Aerosol powders:

Some medicated powders are administered by inhalations with the aid of dry powder inhalers which deliver micronized particles of medication in metered quantities. Most of these products are used in the treatment of Asthma and bronchial disorders, deep lungs for this purpose particle size must be 1 to 6 microns.

Bulk and divided powders:

Ø Divided powders:

After the powder has been properly blended using a geometric dilution method for potent substances. It may be divided into individuals closing units depending on the amounts of medicament taken as single dose.

It includes Bulk powders, antacids and laxatives douches powders and medicated powders for external use.

General methods of preparations of Powders

Since there is a little unavoidable loss of powders during weighing and mixing because some powder will adhere to spatula, pestle and mortar, therefore calculation for one extra powder then required. But if by calculating for extra powder an awkward fraction of weight is involved then a suitable no. of extra powder may be calculated. The dispensing balance is not so sensitive than the quantities less than 2 grains or 130mg must be triturate with a with a suitable inert diluent so that the quantities are made weighable on dispensing balance.

Generally lactose is used as diluent because it is colorless, soluble and compatible with majority of drugs. Mix all ingredients in ascending order of their weighs and mix thoroughly so that a homogenous mixture is formed.

Weight out required no. of powder and wrap in papers. The volatile substance and hygroscopic powders required to be double wrapped. The inner wrapped of which should be of wax paper to prevent volatilization and absorption of moisture.

Powders require special consideration:

The considerations which should be kept under observation for powders are written below;

1.     Hygroscopic and delinquent:

The substances which absorb moisture from the atmosphere are not suitable for dispensing in powder papers because they absorb moisture and promote the chemical degradation of drugs. In case of effervescent preparation the acid may completely react with sodium bicarbonate (NaHCO₃), ammonium chloride (NH₄Cl), sodium bromide (NaBr), sodium iodide (NaI) and talc.

Hygroscopic powders are usually supplied in granular form in order to expose less surface area to atmosphere. They should not be finely powdered. They should be doubly wrapped. In humid weather Aluminum foil or plastic is used.

2.     Eutectic mixtures:

When two or more than or substances are mixed together they tend to liquefy due to the formulation of new compound which has a lower melting point than room temperature for example Acetamide, Methnol, thymol, phencetin, camphor, aspirin, phenol etc.

They may be dispensed as a separate set of powders. They may be incorporated in powder by adding invert absorbent like light magnesium carbonate (MgCO₃) or magnesium oxide (MgO).

3.     Efflorescent powders:

These are crystalline substances that liberate water of crystallization completely or partially due to change in relative humidity or during trituration, causing the powder to become wet or liquefy. This difficulty may be overcome by using either corresponding anhydrous salt or inert substances mixed.

Granular powders

Sometimes it is difficult to present solid medicaments and large suitable forms. The tablets and capsules cannot be prescribed because a large number of them will be required to take a single dose which is not feasible liquids cannot be prepared because of stability problems.Choice remains to powders but bitter nauseous and unpleasant powders are different to dispense as such. These powders are prepared in the form of granules.

Ø Vegetable powders:

Contain volatile oils should not be subjected to heavy grinding in the mortar. When it is necessary to powder them lightly in the mortar to prevent the loss of volatiles oils present in them. In dispensing vegetable powders and other volatile substances they must be doubly wrapped inner wrapper of which should be of wax paper.

Ø Effervescent granules:

These are specially prepared solid dosage form of medicament meant for internal use. They usually contain a soluble medicinal agent mixed with citric acid, tartaric acid, sodium bicarbonate.

Method of preparations of Granules

Granules are prepared by several of the following methods;

§  Heat method

§  Wet method

    Heat method:

A large porcelain or stainless steel evaporating dish is placed over water bath which is being heated to boiling point and must ensure that the evaporating dis is not when the powder are added to it. Failing to do so will not provide sufficient water needed for granulation which will be liberated by citric acid on heating.

    Wet method:

In this method the mixed ingredients are moistened with suitable liquid (for which alcohol is most suitable) in dish in which alcohol is added in small portion with continuous stirring until a coherent mass is formed. The mass is then passed through a no. 6 sieve and the granules are dried on 59⁰C temperature not exceeding 60⁰C.The dried granules are again passed through the sieve break the lumps which may have formed during drying. They are packed in wide mouth air tight containers.

Ø Bulk powders:

They are supplied in bulk quantities and the patient measured the dose according to need. The bulk powders are meant for internal use is supplied in wide mouthed containers in which a tea spoon can be entered easy removal of the contents. Only the non-potent substances are supplied as bulk powders. Example: Antacids, laxatives etc.

Bulk powders meant for external use like antiseptic and dusting powders are supplied in card board glass or plastic containers, which are often designed for specific method of application.

Ø Dusting powders:

These are meant for external appropriate to the skin for antiseptic, antipruritic, antiperspirant, absorbent, protective and lubricant. The powder must be homogenous and in a very fine state of subdivision to enhance the effectiveness and minimize local irritation.

Ø Insufflations:

These are finely divided powders meant for the introduction into body cavities such as ear, nose, vagina, and tooth sockets with the help of an apparatus known as insuff.

Ø Snuffs:

Snuffs are finely divided solid dosage form of medicaments which are inhaled into nostrils for their antiseptic, decongestion or bronchodilators action. Snuffs should be dispensed in flat metal boxes.

Ø Dentifrices:

Dentifrices are the substances which are generally used with the help of tooth brush for cleaning the surface of teeth.

Ø Explosive powders:

When an oxidizing agent and a reducing agent are triturated in mortar then are changes of explosion which may lead of serious consequences, such substances are referred to as explosive powders.

Ø Potent drugs:

Substance having a maximum dose of less than are grain and poisonous substance should be regarded as potent substances. Small quantities of drugs should not be weighed on dispensing balance. The best method to prepare potent drugs is trituration.

Ø Cachets:

Cachets are classical dosage form. Cachets are the solid unit dosage form of medicaments in which the drug is enclosed in a tasteless sheet made by pouring a mixture of rice flour and water between not polished revolving cylinders since flour and water mixture treat easy digestible, disintegrate in stomach.

Advantages of Cachets:

1.       They are easy to prepare because no complicated machinery is required.

2.       Drugs can be extemporaneously and quickly dispensed in cachets.

3.       Comparatively large dosage of drug can be dispensed because one they have been softened by dipping in water even a large size can swallowed easily.

4.       They quickly disintegrate in stomach.