Compounding Suspensions PDF

drugs arenot Dr Mohd Hanif Zulfakar OBJECTIVES ’ After the session, you will be able to: ’ Define and classify the different types of suspensions ’ Describe the pharmaceutical applications, physical properties of a good suspension and the advantages and disadvantages of...

drugs arenot Dr Mohd Hanif Zulfakar OBJECTIVES ’ After the session, you will be able to: ’ Define and classify the different types of suspensions ’ Describe the pharmaceutical applications, physical properties of a good suspension and the advantages and disadvantages of suspensions ’ Discuss the various types of suspending agents ’ Formulate and prepare suspensions 2  INTRODUCTION ’ Suspensions are important pharmaceutical dosage & still being widely used ’ Often used for ‘emergency’ preparations ’ Pharmaceutical products commonly available in suspensions include: ’ Ear drops ’ Enemas for constipation through rectum ’ Inhalations ’ Lotions ’ Mixtures for oral use 3 DEFINITION ’ Suspension is a preparation where at least one of the active ingredients is suspended through the vehicle or pharmaceutical solvents ’ According to British Pharmacopeia (BP), oral suspension is defined as “Oral liquids containing one or greater active ingredients suspended in a suitable vehicle where suspending solids may slowly separate on standing but are easily redispersed 4  Advantages & disadvantages Advantages Disadvantages Insoluble drugs may be more palatable Requires shaking before use Insoluble drugs may be more stable Accuracy of dose less than solution In lessaccuracy Suspended insoluble powders are easier Affected by storage conditions to swallow insoluble powders o Allow for easy administration of bulk Bulky compared to solid dosage forms & exposed to container breakages neetdtoshake.IT Absorption faster than solid form bus we Lotion have cooling effect Sustained-released formulation can be prepared 5  General principles for preparation of suspension ’ Suspensions differ than solutions in terms that one or greater solid ingredients are suspended rather than dissolved in it ’ The abilities to suspend in a vehicle varies among different pharmaceutical solids ’ Therefore, 2 types of pharmaceutical suspension exists: 8 ’ Diffusible suspensions ’ Indiffussible suspensions 6  Eiii Diffusible suspensions ’ Suspensions which contain light powders that are insoluble/only very slightly soluble in the vehicle ’ Dispersed evenly throughout the vehicle upon shaking allowing accurate dose to be dispensed ’ E.g Light Kaolin BP – insoluble in H2O Light Magnesium Carbonate BP-very slightly soluble in H2O Magnesium Trisilicate BP-insoluble in water 7 Indiffusible suspensions ’ Suspensions which contain heavy powders insoluble in the vehicle & upon shaking do not disperse evenly long enough to allow accurate dose to be dispensed ’ Thus the vehicle must be thickened to reduce the rate at which powder settles which is achieved by adding suspending agent ’ Sedimentation rates can also be reduced by  particle size of powder in suspension C D ’ Example of indiffusible powders in pharmaceutical suspensions include Aspirin BP, Calamine BP, Chalk BP, Zinc Oxide BP 8 Formulation ’ Commonly used vehicle is H2O ’ Density of aqueous vehicle can be changed by adding sucrose or glycerol or suspending agent ’ Other additives include colourings & flavouring agents, preservatives ’ Preservatives used in suspensions include Benzoic Acid BP 0.1% (internal use) and Chlorocresol BP 0.1% w/v (extenal use) ’ 9 Suspending agents ’ Natural polysaccharides Acacia BP – gum obtained from stems & branches of acacia tree. Tragacanth- dried gummy exudates from the Astralagus 8 shrub. Less sticky suitable for internal also external products. Used in suspending heavy insoluble powders Sodium alginate- obtained from seaweed. ’ Semi-synthetic polysaccharides Methylcellulose BP – A methyl ether of cellulose 10  Clays Hydrate easily producing gels of varying thickness depending on the concentration used. Prone to contamination thus require preservative. Clays used for pharmaceutical manufacture must be sterilised. E.g. Bentonite Synthetic agents E.g. Carbomer- mainly used for preparations intended for external use Miscellaneous agents Gelatin 11 Suspending agents used in extemporaneous formulation Category Suspending agent Natural polysaccharides Acacia gum BP Agar BP Carrageenan BP Compound Tragacanth Powder BP Guar Gum BP Powdered Tragacanth BP Sodium Alginate BP Starch BP Semi-synthetic polysaccharides Hydroxyethylcellulose BP Methylcellulose BP Sodium Carboxymethylcellulose BP Clays Aluminium Magnesium Silicate BP Bentonite BP Magnesium Aluminium Alginate BP Synthetic agents Carbomer BP Polyvinyl alcohol BP Miscellaneous compounds Gelatin BP 12 Wetting agent ’ May also be added to facilitate suspensions of powders ’ Some powders have tendency to float on surface as air becomes trapped in solid particle preventing them from being dispersed in the vehicle ’ A film of unwettable solid forms at liquid/air interface ’ Wetting agent added will be adsorbed at solid/liquid interface resulting in particles having more affinity for surrounding particle 13  0000 ’ Wetting agents for internal mixtures include polysorbates & sorbitan esters while acacia & tragacanth has also been used ’ Wetting agents for external use include quillaia tincture as in Sulphur Compound Lotion BP or sodium lauryl sulphate 14 “Emergency formulations” ’ Compounders may be requested to prepare a liquid preparation for patients unable to swallow tablet/capsule & sometimes the medicament may only be available as solid dosage form ’ Thus, tablets are usually crushed or capsules opened to provide powdered drug to prepare suspension ’ Tragacanth Powder BP or Compound Tragacanth Powder BP are usually the suitable suspending agent 15 Appropriate tragacanth to use O ’ 0.2 g Tragacanth BP powder for 100ml suspension O ’ 2g Compound Tragacanth Powder BP for 100ml suspension 16 Things to consider in suspension ’ Care should be taken to ensure uniform particle size & dispersion where possible - by purchasing powder from a pharmaceutical manufacturer or tablets are ground to a uniform powder prior to suspending Use of commercially & universally available suspending agents Consider potential sedimentation- specific labelling “Shake well before use” 17  General method for preparation of suspension 1. Check the solubilities in the vehicle of all solids in the mixture 2. Calculate the quantities of vehicle required to dissolve any soluble solids 3. Weigh all solids 4. Dissolve all soluble solids in the vehicle in a small glass beaker 18 5. Mix any insoluble diffusible powders in a porcelain mortar using the “doubling technique” (refer page 25 Guide to Compounding & Dispensing” For insoluble indiffusible powders add also the suspending agent in a porcelain mortar 6. Add a small quantity of the vehicle (which may be the vehicle with the dissolved soluble ingredients) to solids in mortar & mix with pestle to form a smooth paste 19 7. Add further vehicle in small quantities & continue mixing until the mixture reached the state of a pourable consistency 8. Transfer all content of the mortar to a conical flask with final volume noted 9. Rinse out the mortar with more vehicle with rinsings added to the conical measure 10. Add the remaining liquid ingredients to the mixture in conical measure 20 11. Make up to final volume with vehicle 12. Stir gently, transfer to a suitable container ensuring all solid is transferred from conical measure to bottle 13. Label the container ready to be dispensed to patient 21 External use suspensions ’ Need to consider the appropriate choice of suspending agent ’ E.g. Tragacanth Powder BP, Bentonite BP, Methylcellulose BP, Carbomer 22 Inhalations ’ Liquid products that contain volatile ingredients to be E released & brought into contact with respiratory lining ’ Inhalations formulated as suspension allow a useful way of effecting the transfer as volatile ingredient can be adsorbed onto carrier powder (a diffusible solid) then when suspension added to hot H2O the volatile ingredient is released & inhaled by the patient 23 Lotions 000 ’ May be suspensions or solutions or emulsions ’ Intended to be applied for external use only; directly on to the skin without dressing ’ Used to soothe, cool, dry & protect irritated skin & wounds I ’ E.g. Calamine Lotion 8 24 Applications ’ May be suspensions or solutions or emulsions ’ Intended to be applied to the skin without any dressing or covering material 25 Packaging ’ Similar to solutions as both preparation types are based on liquid administration ’ Route or method of administration & suitable container size should be considered in the selection of packaging for extemporaneous prepared suspensions ’ Preparations for oral route should be packed in plain (smooth) amber bottles ’ External preparations should be packaged in fluted amber bottles 26  Discard date ’ Similar to those pharmaceutical solutions ’ An expiry date of 2 weeks is suggested for ‘Freshly Prepared’ preparation or preparations that contain an infusion or vegetable matter ’ A 4 week expiry is applicable to ‘Recently Prepared’ preparation ’ An expiry of 7-14 days are recommended for a suspension that: ’ Do not have preservative ’ Have no information on stability ’ Is new or an ad hoc preparation 27 Labelling ’ The following points are to be considered: ’ ‘Shake the bottle”-all suspensions require this additional label ’ ‘Not to be taken’-must be added to the label of any inhalations ’ ‘For external use only’-must be added to the label of any other suspension not intended for administration via oral route 28 Worked example Mary Lamb, MD 45, Donkey Street Austin, Texas 34000 Tel: 4539990 For Lisa Marie RN: 9052 Date Mac 13 2015 Address 1334 Window Creek AGE: 8 SEX: F Rx Magnesium Trisilicate Mixture BP Sig: 10ml tds Mitte : 150 ml Mary Lamb, MD SN 234987 29  Method Product formula (British Pharmacopeia, 1988, page 740) 1000ml 100ml 50ml 150ml (Master formula) Magnesium Trisilicate BP 50g 5g 2.5g 7.5g Light Magnesium Carbonate 50g 5g 2.5g 7.5g BP Sodium bicarbonate BP 50g 5g 2.5g 7.5g *Concentrated Peppermint 25ml 2.5ml 1.25ml 3.75ml Emulsion BP Double Strength Chloroform 500ml 50ml 25ml 75ml Water BP Potable water to 1000ml to 100ml to 50ml to 150ml *Typically 0.25 – 1 mL per DOSE 30 Step 1 1. Using the master formula from British Pharmacopeia, calculate the quantity of ingredients required to produce the final volume required 31 Step 2 2. Calculate the composition of a convenient quantity of Double Chloroform Water BP 32 Step 3 Weigh 7.5g Magnesium Trisilicate BP Weigh 7.5g Light Magnesium Carbonate BP Weigh 7.5g Sodium Bicarbonate BP Measure 3.75ml Concentrated Peppermint Emulsion BP using a 1ml and 5ml syringe 33 Step 4 The final volume of Magnesium Trisilicate Mixture BP required (150ml) will contain 7.5g of Sodium Bicarbonate BP. As 1g is soluble in 11ml, 7.5g is soluble in 82.5g (7.5 x 11=82.5mL). Therefore a minimum of 82.5ml of vehicle is required to dissolve the 7.5g of sodium bicarbonate. When choosing the amount of vehicle to use for dissolution, important to consider the total amount of each liquid ingredient in the preparation to ensure that only the correct amounts are added or the final product does not go over volume 34 Step 5 Accurately measure 75ml Double Strength Chloroform Water BP using the 100ml measure. To this add approximately 15ml potable H2O in order to produce 90ml of vehicle, which should be poured into a beaker (to produce sufficient volume to dissolve the 7.5g Sodium Bicarbonate BP) 35 Step 6 The Sodium Bicarbonate (7.5g) should be added to the vehicle by principle of adding solutes to the solvents Stir to aid dissolution Transfer the Magnesium Trisilicate to a porcelain mortar Add the Light Magnesium Carbonate BP to the Magnesium Trisilicate BP in the mortar & stir with pestle to ensure even mixing * The Magnesium Trisilicate is added to the mortar first as it occupies the smallest volume & thus the 1st powder to be added to the mortar 36 Step 7 Add a small amount of the sodium bicarbonate solution to the powder in the mortar & mix with pestle to make a smooth paste Continue adding sodium bicarbonate slowly, until paste is pourable Transfer the content of a mortar to 200ml conical measure Rinse out the mortar with more sodium bicarbonate solution & add the rinsings to the conical measure Add the Concentrated Peppermint Emulsion BP to the mixture in conical measure Make up to volume with remaining solution & potable H2O Transfer the solution to a 150mL amber flat medicine bottle with a child resistant closure & label 37 Label Magnesium Trisilicate Mixture BP 150mL Name: Lisa Marie RN: 9052 Take 10mL three (3) times a day Shake the bottle before use Date of dispensing: 13 March 2015 Expiry 9 April 2015 Farmasi UKM, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur 38