Lecture 1: Solid Dosage Forms - Powders and Granules PDF

Lecture 1 Solid Dosage Forms Powders and Granules  Intended Learning Outcomes “ILO’s”  After this lecture the student should be able to:  List the advantages and disadvantages of solid dosage forms compared to other dosage forms.  Identify the types of Powders as a dosag...

Lecture 1 Solid Dosage Forms Powders and Granules  Intended Learning Outcomes “ILO’s”  After this lecture the student should be able to:  List the advantages and disadvantages of solid dosage forms compared to other dosage forms.  Identify the types of Powders as a dosage form.  Identify effervescent granules: advantages and disadvantages.  Identify the advantages of granules over powders.  List the disadvantages of Powders and granules.  SOLID DOSAGE FORMS  Solid dosage forms include; Powders, Granules, Tablets, Capsules and Suppositories.  Advantages of solid dosage forms  1. More chemically stable than liquid, with longer shelf life. 2. Easy shipping and handling. 3. Less needed shelf space. 4. No preservation requirements. 5. Accurate dosage (single dose). 6. Suitable for sustained release preparation.  Disadvantages of solid dosage forms  Their preparation needs complicated and expensive machines.  N.B. powders and granules have a faster dissolution and absorption rate than tablets or capsules  Powders as a Dosage Form  Definitions  Powder as dosage form is a mixture between drug powder and excipients powder in a dry form that may be intended for internal (oral powders) or external (topical or dusting powder) use.  The function of the excipients depend on the intended use of the product e.g. colouring, flavoring and sweating.  Powders as a Dosage Form  Powders are dispensed as :  1- Bulk powder for internal use.  2- Bulk powder for external use (Dusting powders)  3- Divided powder for internal use  4- Divided powder for external use  5- Insufflation powders  6- Dry powder inhalers  7- Antibiotic syrups to be reconstituted before use  8- Powders for injections  1- Bulk Powders for internal use  The mixed ingredients are packed into a suitable bulk container such as a wide-mouthed glass jar to facilitate dosing.  They are used by mixing the directed amount of powder (usually one teaspoonful) in a portion of water before swallowing.  The constituents usually relatively non-toxic medicaments with a large dose.  Many dietary/ food supplements are packed in this way.  2- Dusting Powders  Contain ingredients intended for external use e.g., antibacterial and antifungal powders, or non-medicated powders e.g., Talc powder.  Normally dispensed in perforated, sifter can or an aerosol container  The powder must flow well from such a container, so that they can be dusted over the affected area.  Only sterile dusting powders should be applied to open wounds to avoid the introduction of contaminants and the growth of microorganisms e.g., Canesten Powder (clotrimazole) is used as an antifungal agent  Dusting powders for lubricant purposes or superficial skin conditions need not be sterile but they should be free from pathogenic organisms.  Examples of Bulk container in pharmacy Perforated or sifter can An aerosol container Examples of Dusting powder in pharmacy  3- Divided Powders for internal use  Like bulk powders, but individual doses are separately wrapped.  Traditionally were wrapped in paper but this was unsatisfactory for hygroscopic, volatile or deliquescent ingredients.  Modern packaging materials of foil and plastic laminates have replaced such paper wrappings because they offer superior protective qualities and are amenable to use on high-speed packing machines.  Example: Oral powders in unit dose sachets :These powders are intended for administration after premixing with water or a food product, such a yogurt or juice e.g. the probiotics 3- Divided Powders for internal use  4- Divided Powder for external use Example of Divided powder for external use is Douche powders (e.g. vaginal douche) are dissolved in warm water before application.  5- Insufflation powders  Insufflations  Intended to be blown into regions such as the ear, nose and throat using an insufflator  The use of insufflations declined because:  1- They were not very acceptable.  2- It was difficult to ensure that the same dose was delivered on each occasion with drugs have systemic activity.  To enhance convenience and ensure that a uniform dose is delivered on each occasion, devices have been developed to replace the traditional insufflator.  6- Dry powder inhalers  Developed to deliver the active ingredients to the lung for the treatment of asthma and chronic obstructive pulmonary disease.  Powder used in Dry-powder inhalers should have the following criteria:  1- Good flow  2-Lack of adhesion to the material of package  3-Low and uniform particle size for deposition in the appropriate region of the lung  4- Adequate low drug dose.  Examples of Dry-powder inhalers in pharmacy  Sufficient drug for one dose may be presented in a hard gelatine capsule diluted with an inert, soluble diluent such as lactose. The capsule is placed in the body of the insufflator and is broken when the device is assembled. The drug is inhaled by the patient as a fine powder.  7- Antibiotic syrups to be reconstituted before use  Antibiotic syrups to be reconstituted before use Oral antibiotic; for stability problems the antibiotic is prepared in a dry form (powder or granules) and packed in a sealed bottle, a given amount of water is added before use.  The shelf-life of powders for antibiotic suspension, is 2-3 years, but once it is reconstituted the patient should be warned of the short shelf life (usually 1-2 weeks).  8- Powders for injections  Injections of medicaments that are unstable in solution must be made immediately prior to use and are presented as sterile powders in vial. The powder may contain suitable excipients in addition to the drug, e.g. sufficient additive to produce an isotonic solution when the injection is reconstituted.  Powder Flowability  Process which needs free flowing powders  1- Tablet manufacturing. 2- Dusting powder: to spread easily in the skin  3- Powder with high inter particular friction can not filled into container by automatic filling machine  Powder flowability depends on 1- Particle size 2- Particle shape 3- Adhesion and cohesion 4-Size distribution 5- Moisture content How to increase the powder flowability? 1- Reduce surface roughness. 2- Reduce stickiness by addition of lubricant and glidants ex. Talc , starch and stearic acid 3- granulation.  Powder Flowability  Characterization of powder Flow 1. Bulk Density Method (g/cm3) It is the Ratio of the weight of a powder to the volume it occupies. It is important in determining the size of containers needed for handling, shipping, and storage of raw material and granulation. It depends on particle packing and changes as the powder consolidates. A consolidated powder is more resistant to flow than a less consolidated one. The ease with which a powder consolidates can be used as an indirect method of quantifying powder flow. *It is used to calculate the Hausner ratio.  Powder Flowability  Hausner ratio  The ratio of the tapped density of powder to the bulk density of powder.  Used in a wide variety of industries as an indication of the flowability of a powder.  Hausner ratio = Tapped density / Bulk density  Higher values of the ratio indicate poor flowability of the powder. If the Hausner factor is less than 1.2, this means that the powder has low interparticle friction, i.e., good flowability.  Used to calculate the Carr index  Powder Flowability  The Carr index  The Carr index is frequently used as an indication of the Compressibility of a powder.  In a free-flowing powder, the bulk density and tapped density would be close in value, therefore, the Carr index would be small. On the other hand, in a poor-flowing powder where there are greater interparticle interactions, the difference between the bulk and tapped density observed would be greater, therefore, the Carr index would be larger.  A Carr index greater than 25 is considered to be an indication of poor flowability, and below 15, of good flowability  Powder Flowability 2- Angle of repose  It gives a measure of the frictional forces which oppose the flow of a loose powder.  Angle of repose is the maximum angle possible between the surface of the pile (heap) of powder and the horizontal plane.  The rougher and more irregular surface granules, the higher will be the angle of repose.  Powder Flowability  Factors affecting angle of repose  Rough and irregular surface of the particles give higher angle of repose.  Decrease in particle size leads to higher angle of repose.  Lubricants at low concentration decreases angle of repose whereas high concentration increases angle of repose. So, optimum concentration of lubricants required to maintain angle of repose for good powder flow.  Fines increases angle of repose.  Granules as a dosage form  Definitions  Granules as a dosage form consist of powder particles that have been aggregated to form a larger particle, which is usually 2-4 mm in diameter.  Granules may be used as such granules of therapeutic importance or in tablet and capsule production due to their better followability compared with powders.  This is much larger than granules prepared as an intermediate for tablet manufacture.  granules contain similar medicaments to powders, i.e. those with low-toxicity, high dose drugs. Methylcellulose Granules, for example, are used as a bulk-forming laxative granules  Advantages of granules over powders  1- Better followability  2- Narrow range of particle size so that no segregation.  segregation of powders occurs due to difference in particle size or densities  3- More stable than powder due to less exposed surface area so it is preferred in preparing dry product intended to be constituted like antibiotic.  4- Easily wetted by liquids than light and fluffy powders which float on the surface Granules as a Dosage Form  EFFERVESCENT GRANULES  A solid dosage form meant for internal use. They contain a medicament mixed with citric acid, tartaric acid and sodium bicarbonate. Sometime saccharin or sucrose may be added as a sweetening agent.  This kind of mixtures are dissolved in water and are taken during effervescence or immediately thereafter.  when added to water, the acids and the base react to liberate CO2, resulting in effervescence.  WHY a combination of Tartaric acid and Citric acid is used as an effervescent base rather than either acid alone?  Citric acid is not used alone because it results in a sticky mixture that will not easily granulate. Tartaric acid is not used alone because the granules will be too friable and crumble  Advantages of effervescent granule  1. Attractive dosage form for the public.  2. The carbonated solution masks undesirable taste of the drug.  3. The liberated CO2 gas is used as a therapeutic agent; it increases gastric secretions and hence facilitates digestion, carminative and it acts as antinauseant.  4. Using granules rather than powders decreases the rate of solution and prevents uncontrollable effervescence.  Methods of preparation of effervescent granules  1. Fusion method  The binding agent is the one molecule of water present in each molecule of citric acid.  Powders are weighed and mixed together then placed on a porcelain dish on boiling water bath and stirred with the help of a glass rod.  The heat causes the release of the water of crystallization from the citric acid which in turn dissolves a portion of the powder mixture, setting of the chemical reaction and the consequent release of some carbon dioxide. This causes the softened mass of powder to become some what spongy, and when of the proper consistency (as bread dough) ,it is removed from the oven and rubbed through an acid resistant sieve to produce granules which are dried at temperature not more than 54 C , transferred to containers and tightly sealed.  The fused method is used in the preparation of most commercial effervescent powder.  Methods of preparation of effervescent granules  2. Wet method  In this method all the ingredients are mixed together with non aquous vehicle usually alcohol to prepare a coherent mass which is then passed through sieve to obtain the desired size of granules.  The obtained granules are dried at oven at 60 C.  The dried granules are again passed through the sieve to break the lumps which may be formed during drying.  The dried granules are packed in air tight container.  Powders Granules Poor flow properties Good flowability Less stable due to large surface area More stable More likely to cake formation on long storage Less likely Poor compressibility good Possibility of non uniform dosing is more less  Storage precaution  All powders and granules should be stored in a dry place to prevent deterioration due to moisture. Even if hydrolytic decomposition of susceptible ingredients does not occur, the particles will adhere and cake, producing an inelegant, often unusable product.  N.B. It is important to protect effervescent granules from moisture during manufacture and storage to prevent premature reaction between acids and base.  The Disadvantages of powders and granules  1. Bulk powders or granules are less convenient for the patient to carry.  Solve: Using heat-sealable laminated sachets and individual doses.  2. Problems with masking the unpleasant tastes.  Solve: Add sweating agent or formulate taste-masked effervescent product.  3. Bulk powders or granules are not suitable for administering potent drugs with a low dose due to variation in spoon fill and variation in the bulk density of different batches of a powder.  Solve: Divided preparations have been used for more potent drugs, but tablets and capsules have largely replaced them for this purpose.  4. Not a suitable for drugs which are inactivated in, or cause damage to, the stomach  Solve: Formulated as enteric-coated tablets.