Student Practical Guide (1) Milk of Magnesia

Transcription

1 School of Pharmacy Student Practical Guide (1b) Milk of Magnesia Facilitators Dr Mark Hewitt Required Resources Pre-work: Read this guide Dr Rebecca Butler Compulsory: Appropriate clothing and shoes Lab coat (will be provided) Safety spectacles (will be provided) Learning Outcomes 1. Be able to work safely in a laboratory 2. Be able to prepare magnesium hydroxide mixture (milk of magnesia) : Milk of Magnesia 1

2 Good Laboratory Practice A practical session is great fun and an excellent learning experience but it is important that you listen and are sensible at all times. It is essential that you are suitably dressed for practical sessions. We expect: Flat/Low heels with closed toes (and socks to ensure no exposed skin). No Large/Dangly earrings. Small sleepers/studs only. Hair tied back. Head scarves tucked into lab coats. You must not eat, drink or chew gum. You will be provided with and must wear a lab coat and safety goggles. (N.B. Spectacles are not a substitute) You must use gloves when instructed. : Milk of Magnesia 2

3 Preparation of Milk of Magnesia Introduction The aim of this practical is to provide you with an insight into pharmaceutics and the extemporaneous preparation of pharmaceutical products. Preparation of products in the pharmacy is something that is still seen but, increasingly, these products tend to be ordered from specialist pharmaceutics suppliers. Extempor-what?? Not all medicinal products are available off the shelf. Extemporaneous preparation (or manufacture) refers to the process by which a pharmacist produces a medicinal product to meet the special needs of a patient, or group of patients, when no suitable licensed medicinal product is available. Such products (often referred to as specials ) may be developed to address patient sensitivities to particular excipients within off the shelf alternatives (e.g. lanolin). Often, they are also prepared in order to provide tailored dose preparations for children or other patient groups. Since it is possible to prepare thousands of medicinal products in this manner, it is important that each pharmacy or pharmaceutical manufacturer is consistent in producing an appropriate, safe product. In order to achieve this, the British Pharmacopoeia (BP) has been developed as a reference text which contains a monograph for thousands of pharmaceutical products. Each monograph contains information on how to identify, prepare and test a particular preparation. A script coming into the pharmacy will specify if it is a BP product by having BP at the end of the item description. For example, magnesium hydroxide mixture BP. This indicates that the item has been (or needs to be) prepared according to the BP monograph. In this practical you will be preparing magnesium hydroxide mixture, commonly known as milk of magnesia. Milk of magnesia is commonly taken orally as a laxative to relieve occasional constipation, upset stomachs and also as an antacid to relieve indigestion and heartburn since it will reduce the amount of acid in the stomach. Milk of magnesia is an example of an oral suspension. This means that the hydrated magnesium oxide (magnesium hydroxide) is not soluble in water but is dispersed (suspended) within it. Therefore, suspensions can be a useful way of formulating APIs with poor water solubility. Additional excipients can be added to the suspension in order to improve taste or to slow down the rate of sedimentation. : Milk of Magnesia 3

4 During the practical class you will prepare the magnesium hydroxide mixture using the BP monograph as a guide. You may be using glassware that is new to you (conical measures, Buchner funnels, etc.). If you are unsure on how to use these appropriately, ask a member of staff. You will need to put this product into a suitable labelled container. What information do you think needs to be on a label? Work in Pairs Throughout Equipment 50 cm 3 measuring cylinder Spatula Glass rod 250 cm 3 beaker 500 cm 3 beaker Conical measures Analytical balance (and weighing boats) Light magnesium oxide Sodium hydroxide pellets Magnesium sulphate Buchner funnel, clamp, stand and filter paper Containers (to receive 100ml) Labels Gloves Procedure Step 1: Extemporaneous Preparation of Magnesium Hydroxide Mixture At the end of this lab handout you are provided with the BP monograph for magnesium hydroxide mixture. Typically, this is made in the pharmacy in 1000cm 3 batches. Rewrite the method given in the BP monograph as a series of steps in the space below, adapting it where necessary in order to: Make 100 cm 3 of magnesium hydroxide mixture (not 1000 cm 3 ) Remove chloroform from the formulation (e.g. just ignore it!) Use Buchner filtration rather than a calico strainer (You will need to filter in two stages to prevent the filter paper from becoming blocked) Wash three times with water rather than testing for sulphate Clearly state the amount of each ingredient that is required. Magnesium sulphate (4.75 g) Sodium hydroxide (1.5 g) Light magnesium oxide (5.25 g) Purified water, freshly boiled and cooled; sufficient to produce (100 cm 3 ) : Milk of Magnesia 4

5 Extemporaneous preparation Dissolve the sodium hydroxide in 15 ml of purified water Add the light magnesium oxide, mix to form a smooth cream and then add sufficient purified water to produce 250 ml. Pour this suspension in a thin stream into a solution of the magnesium sulphate in 250 ml of purified water, stirring continuously during the mixing. Allow the precipitate to subside, remove the clear liquid. Filter in two batches using a Buchner filtration system and wash with water the solid with water and allow drying under vacuum Mix the washed precipitate with purified water, to produce 100 ml. Ensure you are wearing a lab coat, safety goggles and gloves Using the equipment provided follow your modified method to make 100 ml of magnesium hydroxide oral suspension Labelling of your product Draw your label here: Following feedback at the end of the session what would you change? : Milk of Magnesia 5

6 Questions: 1) Why does the BP monograph include assays? 2) Is your Magnesium Hydroxide Oral Suspension safe for patients? Explain your answer. : Milk of Magnesia 6

7 British Pharmacopoeia Monograph Magnesium Hydroxide Mixture Magnesium Hydroxide Oral Suspension Definition Magnesium Hydroxide Mixture is an aqueous oral suspension of hydrated magnesium oxide. It may be prepared from a suitable grade of Light Magnesium Oxide. Extemporaneous preparation The following formula and directions apply. Magnesium Sulphate Sodium Hydroxide Light Magnesium Oxide Chloroform Purified Water, freshly boiled and cooled 47.5 g 15 g 52.5 g 2.5 ml Sufficient to produce 1000 ml Dissolve the Sodium Hydroxide in 150 ml of Purified Water, add the Light Magnesium Oxide, mix to form a smooth cream and then add sufficient Purified Water to produce 2500 ml. Pour this suspension in a thin stream into a solution of the Magnesium Sulphate in 2500 ml of Purified Water, stirring continuously during the mixing. Allow the precipitate to subside, remove the clear liquid, transfer the residue to a calico strainer, allow to drain and wash the precipitate with Purified Water until the washings give only a slight reaction for sulphates, Appendix VI. Mix the washed precipitate with Purified Water, dissolve the Chloroform in the mixture and add sufficient Purified Water to produce 1000 ml. The mixture complies with the requirements stated under Oral Liquids and with the following requirements. Content of hydrated magnesium oxide, calculated as Mg(OH) to 8.35% w/w. Characteristics A white, uniform suspension which does not separate readily on standing. Heavy metals Dissolve 12.5 g in 10 ml of hydrochloric acid and 20 ml of water, add 0.5 ml of nitric acid, boil to remove any carbon dioxide and filter. To the cooled filtrate add 2 g of ammonium chloride and 2 g of ammonium thiocyanate and extract with two successive 10 ml quantities of a mixture of equal volumes of isoamyl alcohol and ether. To the aqueous layer add 2 g of citric acid and sufficient water to produce 50 ml. 12 ml of the resulting solution complies with limit test A for heavy metals, Appendix VII. Use lead standard solution (1 ppm Pb) to prepare the standard (4 ppm). : Milk of Magnesia 7

8 Sulphate Dissolve 2.5 ml in 20 ml of hydrochloric acid and dilute to 500 ml with water. 15 ml of the solution, filtered if necessary, complies with the limit test for sulphates, Appendix VII (0.2%). Assay Mix 10 g with 50 ml of water, add 50 ml of 0.5M sulphuric acid VS and titrate the excess of acid with 1M sodium hydroxide VS using methyl orange solution as indicator. Each ml of 0.5M sulphuric acid VS is equivalent to mg of hydrated magnesium oxide calculated as Mg(OH) 2. Storage Magnesium Hydroxide Mixture should not be kept in a cold place. Labelling The label indicates the pharmaceutical form as 'oral suspension'. References BRITISH PHARMACOPOEIA COMMISSION, British Pharmacopoeia. London: TSO. : Milk of Magnesia 8