Pharmaceutics 1: Physiochemical Science and Medicines Design (PHAR1027) - Powders PDF

PHARMACEUTICS 1: PHYSIOCHEMICAL SCIENCE AND MEDICINES DESIGN (PHAR1027) TUNG WH POWDERS  Lecture Overview What is... Stability and storage Small scale manufacture practicals  POWDERS The Simplest Dosage Form  Powders Definition - A solid material in a finely di...

PHARMACEUTICS 1: PHYSIOCHEMICAL SCIENCE AND MEDICINES DESIGN (PHAR1027) TUNG WH POWDERS  Lecture Overview What is... Stability and storage Small scale manufacture practicals  POWDERS The Simplest Dosage Form  Powders Definition - A solid material in a finely divided state. Dosage form that consists of mixtures of powdered DRUGS with or without other excipients to produce final products. Conventionally, “powder” restricted for INTERNAL use – “oral powder” Alternative titles, eg. dusting powder, for external use.  Categories of powders Traditionally dispensed as 1. Bulk oral powders 2. Single dose oral powders (divided powders) - Wrapped powders - (Hard shell) capsules - Tablets (compressed powder) 3. Bulk external powders (dusting powders) Other preps include 1. Insufflation for administration to ear, nose, throat 2. Dry powder inhalers 3. Antibiotic syrup reconstitute before use 4. Powder for injections  1. Bulk Oral (Undivided) Powders A convenient way of giving a drug with large dose, by mouth. The patient takes 5mL spoonfuls of powder, mixed with water or milk. Sold in wide-mouth jars or boxes, with measuring spoon. Useful for non-potent/non-toxic bulky drugs with a large dose eg. antacids.  Rare - inconvenient to carry & possible inaccuracies in measuring dose. Example prep – indigestion remedies/bulk laxatives that requires several grams to be effective eg. Methylcellulose granules (1-4 gm daily), compound Mg trisilicate oral powder, dietary food supplement. Sodium Bicarbonate BP  Pros and cons for bulk oral dose Advantages 1. May be more stable than liquid equivalent 2. Convenient form to dispense drug with large doses, eg. Mg trisilicate dose 1-5g 3. Administered with relative ease, easier to swallow than tablets 4. Generally dispersion and absorption faster than capsules or tablets 5. Flexible dosage form – easy to prepare Disadvantages 1. Bulky and inconvenient to carry 2. Difficult to mask unpleasant taste (sprinkle on food) 3. Inaccurate when administering potent drugs with a low dose - due to usage of the 5mL spoon (tab & capsule more appr) 4. Not suitable for administration of drugs which are inactivated or cause damage to stomach (enteric-coated tablets more appr) 5. Not suitable to dispense substances that are volatile, deliquescent, hygroscopic or O2 – sensitive.  2. Single dose oral powders / divided powders Formulation = bulk powders A convenient way of giving an accurate single dose of drug. 1. Wrapped Powders - for substances administered in controlled dosages (small amount of drug) - single doses of powder wrapped in paper or foil sachets Foil sachets – provide better protection  Paper sachets - easier to make on a small scale - convenient dosage form for children doses of drugs not commercially available - specifically prepared in hosp for babies/infants/ elderly - mix with a liquid (usually water) before swallowing - unsuitable for hygroscopic, volatile and deliquescent substances. - Eg. Antacid, dietary products, effervescent powders, hot or cold drink remedies. Powders in Sachets  Pros and cons of unit dose powders Advantages as dosage forms 1. More stable than liquid dosage forms 2. Accurate dosing 3. Easy to administer 4. Small particle size of drug 5. Acceptable to patients Disadvantages 6. May be difficult to swallow 7. Hard to mask unpleasant flavours Single dose oral powders / divided powders 2. (Hard) Capsules - single doses of powder enclosed in a two part shell - of different sizes - usually made of gelatin (animal bones, skins, etc) - Halagel - halal gelatin product - Convenient and easy to swallow, cost effective on a large scale Powders in capsules  Single dose oral powders / divided powders 3. Tablets - Single dose of powder compressed by a machine - Only made on a large scale (Year 2 practical) using tabletting machine - Excipients added : diluents or fillers - make tablet easier to handle, eg. lactose binders or adhesives - form granules to improve flow properties of mixture & compression, eg. acacia, starch disintegrators or disintegrating agents - ensure tablet breaks down into its component particles after ingestion, eg. sodium alginate antiadherents, glidants, lubricants or lubricating agents - essential for flow of tablet material into the tablet dies & prevent sticking of compressed tablet in the punch & die, eg. magnesium & calcium stearate Tablet s  3. Bulk external powders Dusting powders – bulk powders which are applied to skin For external use – for therapeutic, prophylactic and lubricant purposes – skin diseases, surgical glove lubrication. Sterile dusting powder for open wounds. This Should be free from pathogenic organism. athlete’s May contain one or more medicaments mixed with foot an inert diluent (eg. purified talc, starch or kaolin) powder contains  active ingredient only needed at low conc, hence talc and diluent required (materials with good flow properties). starch Packed in a ‘talcum powder’ style puffer bottles Examples - Hexachlorophene dusting powder (antibac prep) - Talc dusting powder (lubricant to prevent chafing)  4. Drug powder inhalers Most effective method to deliver drugs to the respiratory tract. For treatment of asthma, chronic obstructive pulmonary diseases (COPD). Commercial prep and dry powder devices Eg. Turbohaler ® (Terbutaline) Diskhaler ® (Salbutamol) Becotide ® (Beclomethasone dipropionate)  5. Antibiotic syrup Many drugs are chemically and physically unstable when formulated as solution or suspension. To overcome this – manufacture powder or granules, pack into suitable containers (shelf life at least 2 years). Add H2O to powder/granules immediately prior to supply/use (shelf life 2 weeks).  6. Powder for injection Certain medication unstable in solution. Product – sterile powder packed in ampoules/vials. Prior to use, add sterile H2O (Water for Injections BP) to produce required drug concentration.  Stability and storage Dry powder dosage forms generally more stable than liquid dosage forms but ingredients can be Hygroscopic – absorbs moisture (↑ humidity environment) to form wet mass Deliquescent – absorbs moisture and dissolves in it Efflorescent – powder of hydrated salts loses H2O of hydration (↓ humidity environment) to form wet mass. Eutectic – powder liquefies when mixed – melting point of powder mixtures lower than that of each powder. eg. Menthol + camphor  liquefy  Discolouration – changes colour Caking – absorbs moisture and sticks together Heat degradation – heat may accelerate physical and chemical changes. Hence put on the label STORE TIGHTLY CLOSED IN A COOL DRY PLACE  Packaging Bulk oral powders - glass, plastic, metal or other containers with a wide mouth  allow use of a powder measure Divided powders (oral) - in sachets (during large scale manufacturing) - in powder papers (individually folded) Topical powders - in suitable sized containers Mixing powders : General method Aim Even dispersion of all ingredients within the powder mixture Problems Powders have different particle sizes  may cause separation at a later time. Powders may be present at diff amount. The amount required of one ingredient may be below the accuracy limit of the balance.  The Pestle & Mortar Pestle Mortar Used for mixing as well as grinding  Mixing powders : General Method Comminution of drug Mixing of powder Packaging of powder 1. If particle size looks grossly diff grind the powder. 2. Sieve a slight excess of each powder and THEN weigh them out. 3. Mix powders in mortar and pestle. 4. Put ingredient with the smallest volume into the mortar. 5. Add equal volumes of the other ingredients. 6. Mix gently but thoroughly until an even mixture is obtained. Loosen powder sticking to the side of the mortar with a spatula. 7. Repeat stages 4, 5 and 6 until all the powders are incorporated.  Why mix powder this way? Sieve before weighing since powder is lost on the sieve and the bench. If sieve after weighing, we would lose some of the final products. Could lead to underdosage. Mixing equal volume of powders is the quickest way to ensure an even mix. ALWAYS SIEVE POWDERS Some terms… Mixing in a mortar this way = trituration This method of mixing powder is also known in diff terms - geometric mixing - doubling up - the method of increasing proportions  Golden rules of mixing powders Never weigh amount less than the accuracy limit of the balance. In our lab the accuracy limit is 100mg. Equalise particle size by grinding and sieving if necessary. Mix by geometric mixing, but don’t attempt a powder mix of greater than 1 in 10.  Wrapping Powders There are several ways of wrapping powders. A suitable size is 120mm x 100mm. Carry out the wrapping on a clean tile or a large sheet of the wrapping paper to protect the product. See video of powder wrapping  Further Reading 1. AJ Winfield & RME Richards (2004). Pharmaceutical Practice. 3rd Edition. Churchill Livingstone. Chapter 22. 2. ME Aulton (2007). Aulton’s Pharmaceutics. The Design and manufacture of medicines. 3rd Edition. Churchill Livingstone/Elsevier. Chapter 28. 3. Loyd V Allen Jr (2002). The Art, Science and Technology of Pharmaceutical Compounding. American Pharamceutical Association. Chapter 9.