Inorganic Medicinal Compounds 2 PDF

PHAR 1112 Pharmaceutical Chemistry Inorganic Medicinal Compounds 2 © 2019, University of Cyberjaya. Please do not reproduce, redistribute or share without the prior express permission of the author.  PHAR 1112 Pharmaceutical Chem...

PHAR 1112 Pharmaceutical Chemistry Inorganic Medicinal Compounds 2 © 2019, University of Cyberjaya. Please do not reproduce, redistribute or share without the prior express permission of the author.  PHAR 1112 Pharmaceutical Chemistry Inorganic Medicinal Compounds 2: Pharmaceutical Aids and Necessities Learning objectives 1. Discuss the different classes of pharmaceutical aid with suitable examples. 2. Explain the properties and uses of sodium bisulphite and purified water. remember some /al example. Introduction Pharmaceutical aids could be either organic or inorganic chemicals that have very little or no therapeutical value. However, these chemicals are necessary in the manufacture of various so dosage form, e.g., ointments, orals, tablets, liquids, injectables. add Apl + mineral i phanm aids. They might be required for purposes as preservation, stabilisation, acidification or alkalisation, suspending, excipient, adsorption, absorption, filtration, prevention of oxidation, complexation, etc. Pharmaceutical aids are also referred to as pharmaceutical necessities. Introduction Gaction PharmaceuticalC aids may remain in the final product, where they do not exert any specific action on the body when the product is administered. They could also be removed during processing but come in close contact with the product at some stage. Thus, it is essential for pharmaceutical aids to be of some quality as therapeutic agents and are subjected to similar quality controls. The various pharmaceutical aids could be classified into categories as listed next. included as pharoscoped & monograph Classification of pharmaceutical aids into various categories 1. Acidifiers and alkalisers 2. Buffers 3. Absorbents and adsorbents 4. Antioxidant and preservatives 5. Desiccants 6. Excipients 7. Suspending agents 8. Filter aids Classification of pharmaceutical aids into various categories 9. Colourants 10. Tonicity adjusting agent 11. Solvent and vehicles 12. Colouring, flavouring and sweetening agents 13. Ointment and suppository bases 14. Diluents, binders, disintegrating agents and lubricants 15. Solvents or vehicles Acidifiers and alkalinizing agents ↓ define Substances which are used for changing the reaction (pH) of a liquid product or maintaining the pH of the product. Only such acids, alkalies and their salts are to be used which do not exert any harmful effects on the body. Alkalinising agents are also called alkanisers. Gestomach Example: hydrochloride acid, dilute hydrochloric acid, sulphuric acid, dilute sulphuric acid, phosphoric acid, dilute phosphoric acid, ammonia solution strong, ammonia solution dilute, sodium hydroxide, calcium hydroxide. Buffers & certain pH ~ maintain stability Solutions consisting of a mixture of an acid and one or more of its salts, or vice versa, in a suitable proportion and having a definite pH. The system is able to resist change in pH when small quantities of acidic or basic substances are added. Solutions of drugs in buffers are able to retain their pH and remain stable longer. It is possible to prepare buffers either by mixing stock solutions of the ingredients or by dissolving a solid mixture (powder, pellets or tablets) of these in definite amount of water. Example: hydrochloric acid buffer, acid phthalate buffer, neutralised phthalate buffer, phosphate buffer, alkaline borate buffer, ammonia buffer. Absorbents and adsorbents Absorption: when a substance gets uniformly distributed throughout another substance by a process of diffusion. Absorbent is the substance which is capable of absorbing. If in a similar process the concentration increases on the surface of another substance, but not distributed throughout the other, the term adsorbent is employed. Both these processes occur due to physico-chemical forces. Chemical rxv : substrate material Chemical reaction & No chemical reaction is involved. other material : remain The absorbed or adsorbed material can be released or recovered by employing desorption processes. adsorbent 00000 I100 & ex : 02 + RBC · ou oabsorbent o - - catalyst speed up sponge reaction (adsorbent) - - Absorbents and adsorbents a for diarrhea - adsorb toxins from bacteria production Activated charcoal – acts as a powerful adsorbent, for decolourising and adsorption of dyes. Soda lime – absorbing CO2, finds use in surgical operations in reducing the CO2 content of respired air by patients. Aluminium sulphate – antiperspirant and purification of water by flocculation. Aluminium phosphate – absorbing bacterial toxoids in the preparation of vaccines. Antioxidants and preservatives ↓ chemical reaction The pharmaceutical preparations having readily oxidisable substances or groups get deteriorated on storage due to atmospheric oxidation. product change after oxidation An antioxidant is an agent which is added to such a preparation to prevent oxidation and subsequent deterioration of the product. Antioxidants function chemically as reducing agents. The antioxidant themselves or their reduction products should not be toxic and harmful to human body. In order to achieve prolonged stability, the oxidation of antioxidants should be slow but should be more readily oxidised than the drugs which they are to protect from oxidation. Antioxidants and preservatives It is possible to achieve the antioxidant action by 2 different mechanism: API ~ a - Antioxidant gets oxidised - in place of active drug constituent, or - If the active constituent is oxidised, the antioxidant reduces it back to v state by reducing it (because antioxidant its normal oxidation. - reducing agen perties Selection of antioxidant: - The chances of the desired redox reaction taking place. - It should be effective in low concentrations. & antioxidant > Ap - Physiological and chemical compatibilities. - It must be physiologically inert on the concentration being used. - The possible toxicity of both the reducing agent and its oxidised product. - The solubility with the drug. Antioxidants and preservatives There are several antioxidants which may also have mild bactericidal or bacteriostatic activities. The term preservative is also applied to some of these substances. ge-hydrogen Some important official antioxidant includes sodium sulphite, sodium bisulphite, sodium metabisulphite, sodium thiosulphate, hypophosphorous acid, sodium nitrite, nitrogen, carbon dioxide. Antioxidants and preservatives Sodium bisulphite Chemical formula: NaHSO3, molecular weight: 104.06. Synonym: sodium hydrogensulphite, sodium acid sulphite, sodium pyrosulphate. The official sodium bisulphite consists of sodium bisulphite and sodium metabisulphite (Na2S2O5) in varying proportions. It yields not less than 61.6% and not more than 67.4% of SO2. It is usually prepared by passing sulphur dioxide into a solution of sodium carbonate until the solution is saturated. Na2CO3 + H2O + 2SO2  2NaHSO3 + CO2 Physical properties. It occurs as a white, granular powder or as white crystals. It has an odour of SO2 since it is somewhat unstable in air. It is freely soluble in water but slightly soluble in alcohol. Sodium bisulphite Chemical properties. The bisulphite is neutralised by adding acids to yield sulphurous acid which is the solution of sulphur dioxide in water. NaHSO3 + HCl  NaCl + H2SO3 H2SO3 ⇆ H2O + SO2 H2Supe sulfuric a Pharmaceutical uses. It is used as an antioxidant and stabilizing agent. Usually about 0.1% is sufficient for most purposes. It finds use in epinephrine hydrochloride, phenylephrine hydrochloride and ascorbic acid injections. Converts menadione (synthetic analogue of vitamin K) which is a practically water-insoluble organic compound to a very water- soluble menadione sodium bisulphite compound without involving significant loss of activity. It is also used to solubilize kidney stones. It is also used (0.3 – 0.6 g dose) for its effect as an antiseptic in gastric fermentation and externally as application in parasitic skin diseases. It can also be used for removing permanganate stains and for solubilizing dyes and other chemicals. DAD A Desiccants sel Desiccants: substances that absorbs moisture and provide a dry micro-atmosphere in containers used in keeping pharmaceutical preparations. Some desiccants, when absorb moisture get liquefied or form solutions. Example calcium chloride. Cac + & Some are able to retain rigid crystalline form even after absorbing moisture. Example silica gel. C Used in containers for tablets and capsules which may be opened several times. Excipients Substances used for increasing bulk of a solid mass which carries a drug. Used in the formulation of tablets, capsules, powders, granules and pills. PCM tab = & 500gm entirely ~ buck : excipient Excipients may also be considered as diluents. Do not exert therapeutic action and are generally considered as inert. They also include other non-therapeutic additives used in the formulation of solid dosage forms. They may be described by such terms such as: lubricants, fillers, binding agents, disintegrants, coating agents, etc. all of which are inert. The term also includes anti-oxidants, preservatives, buffers etc. which are active but not therapeutically. Excipients Excipients also enter the body along with the drug. comply with strict Hence, these are needed to conform to the same-stringent measures of quality as therapeutic agents. Some examples of excipient includes: - Tricalcium phosphate - Dibasic calcium phosphate - Magnesium stearate - Purified talc - Calcium carbonate - Calcium sulphate Magnesium stearate Lexcipient It is prepared by neutralising commercial stearic acid (which contains some palmitic acid) and magnesium oxide by heating. Thus, a mixture of magnesium stearate and magnesium palmitate is obtained. Containing about 7.5% of magnesium oxide. (C17H35COO)2 Mg (stearate) and (C15H33COO)2.Mg (palmitate) o like flour very smooth It occurs as a C very fine, white fluffy powder, greasy to touch and free from grittiness, an is having a faint characteristic odour. It finds use as dusting powder in cosmetics, for skin preparations including barrier creams. It is popularly used as lubricant in tableting. Calcium stearate is also used in a similar manner. It is almost non-toxic. Suspending agents and emulsifying agents formulated & Lwhy ? Some dog O Some - 2 one phace phases Includes substances which are described as ‘thickening agents’ or ↓ EA incorporated ‘emulsifying agents’ or ‘stabilising agents for suspensions’. 2 phaces tgt An emulsion may be defined as an intimate mixture of 2 immiscible phases which is stabilised by adding an intermediate substance called emulsifying agent. This emulsifying agent may also be defined as an inert substance which is used to homogenise phases by lowering surface tension. A suspension may be defined as a dispersion having finely divided insoluble material suspended in liquid media. Generally, a substance must be added for overcoming agglomeration of the dispersed particles and for increasing the viscosity of the medium so that the particles settle down very slowly. Such a substance is called a suspending agent. Suspending agents and emulsifying agents Both emulsifying and suspending agents find extensive use in the formulation of numerous pharmaceutical preparations. It is to be noted that there are many compounds which may act both as emulsifying and suspending agents. Commonly used emulsifying and suspending agent includes bentonite, colloidal silica and aluminium stearate. https://www.gcsescience.com/o77.htm https://www.imdip.com/2021/07/suspension-definition- classification-advantage-disadvantage-preparation- methods.html Filter aids They are inorganic substances which are used in clarification processes, especially to hold back fine particles, which may pass through the usual filter media like cloth and paper. Liquid pharmaceutical dosage forms can be clarified by addition of suitable amounts of filter aids for this purpose. Some filter aids are having capacity to adsorb dissolved substances from such solutions. Dissolved substances may include colouring and flavouring agents but also potent drugs. This may bring about not only loss of potent drugs but alter the formulation, supplying less dose of therapeutic agents. Hence, care must be taken in making use of filter aids. Filter aids Moreover, some filter aids can change the reaction of the solution (pH) being clarified, which may be undesirable. The filter aids come in contact with the therapeutic dosage forms during processing. Therefore, these are also subject to stringent quality control. Example includes kieselguhr, Fuller’s earth, light kaolin and talc. Colourants This category also includes compounds which are described as ‘tinting’ agents and ‘opacity’ agents. Includes titanium dioxide and ferric oxides (red and yellow). Titanium dioxide It is included in the pharmacopoeia as topical protectant and pharmaceutical aid. It finds use as ‘opacity agent’ for capsules due to its high reflectance. For the same reason it also acts as a whitening agent, when included in tablet coating formulae and creams and other cosmetics. The high reflectance includes the harmful UV rays, thus facilitating its inclusion in sun protection topical preparations. Tonicity adjusting agents ① Agents used to adjust the tonicity of injectable preparations. Null Sodium chloride most extensively used. - Silver nitrate can be used in eye drops. Also, other suitable salts such as sodium nitrate or sodium sulphate. Solvent and vehicle These are the important pharmaceutical aids, which are used for bringing the drugs in liquid dosage forms. An inorganic compound used for this purpose is water, whose preparation and quality are of great significance because water is used not only for topical purposes (oral and external) but also for injectable (parenteral) products. Example includes purified water, water for injection and sterile water for injection. Purified water In pharmaceutical industries and hospitals, large quantity of water is required for washing of containers and bottles, preparation of pharmaceuticals for oral, external and parenteral administration. ↑ different Ho ! get = distilled H20 Preparation. May be obtained by treatment of water. Distillation: removes ↑ remove mineral dissolved gases. Ion-exchange treatment: deionisation or demineralization. Reverse osmosis: do not need energy or chemical treatment. => mineral #20 - > 0 mineral Description. It is a clear, colourless, odourless and tasteless liquid. Tests for purity. It is tested for copper, iron, lead, Cl-, SO4-, albuminoid ammonia, ammonia, oxidisable matter and non-volatile matter. Test for copper, iron and lead. It is performed by adding one drop of sodium sulphide solution to 100 ml of purified water. The liquid should remain clear and colourless. Purified water Test for oxidizable matter. It is carried out by boiling 100 ml of purified water with 3 ml of H2SO4 and 1 ml of 0.01 M KMnO4 for 10 minutes. The colour of KMnO4 does not get completely discharged. Test for non-volatic matter. It is carried out by evaporating the sample to dryness on water bath and then to constant weight at 105˚C. The residue ~ can use is not to be more than 0.001% w/v. oreach ~ chloride ↑ limit ~ change = impurities Test for chloride. It is carried out by adding to 100 ml of purified water 1 ml of solution of silver nitrate and keeping it for 5 minutes undisturbed. The a O chloride liquid should remain clear and colourless. Test for sulphate. It is carried out by adding 1ml solution of barium chloride to 10 ml of purified water and allow to stand for 5 minutes. The liquid should remain clear and colourless. Colouring, flavouring and sweetening agents Colouring agents In order to increase the aesthetic appearance of pharmaceutical preparations, certain colours or colouring agents are added to the preparations. However, only those colours which are safe and prescribed by the ‘drug and cosmetic act and rule’ must be employed. The minimum concentration used may be 0.001% w/v. Flavouring agents A flavouring agent or a flavour is a complex mixture of aromatic compounds, which are blended to form a body which tends to improve the palatability of dosage forms. In some cases, a single ingredient is added to get a desired flavour. Ointment and suppository bases Ointments may be defined as semi-solid preparations which are used for external application of such consistency that they may be easily applied on skin. Their composition has been such that the tend to soften surface but not necessarily melt when applied to the skin. The inert bases which are obtained by mixing different materials in appropriate proportions for dispersing active medicament in semisolid formulations are termed as ointment bases. Ointment and suppository bases The various characteristics for a substance to be acting as an ointment base are as follows: - It should be compatible with the skin. - It should be stable, permanent, smooth, non-irritating and inert. - It should be able to absorb water or other liquid preparations. - It should readily release the incorporated medicinally active compound. Ointment and suppository bases Ointments bases have been grouped according to their composition into 4 types as follows: - Oleagenous ointment bases I decoder - Absorption ointment bases monograph of ston - Emulsion type ointment bases - Water soluble ointment bases Suppositories may be defined as solid dosage forms which are generally medicated, for insertion into rectum, vaginal cavity or urethral tract. After insertion they may melt or undergo dissolution in the secretions of the cavity. The substances used in the formulation of suppositories are termed as suppository bases. Diluents, binders, disintegrating agents and lubricants Diluents: diluting agents to increase the bulk. Binders: substances which are used for imparting cohesive properties to powdered materials. They are used for granulation. Disintegrating agents: a substance or a mixture of substances which tend to facilitate the breakup of a tablet. Lubricants: substances which are added to improve the rate of flow of granules and prevent adhesion or cohesion during the tablet manufacturing. Solvents or vehicle There are several substances which are used in pharmaceutical formulations as solvents or vehicles. Thank you Address Telephone Website University of Cyberjaya 03 - 8313 7000 www.cyberjaya.edu.my Persiaran Bestari, Cyber 11, 63000 Cyberjaya, Facsimile Email Selangor Darul Ehsan, Malaysia. 03 – 8313 7001 [email protected]