Lecture 2 Powder Dose Forms PDF

PHMD 1012 1 EXTEMPORANEOUS PHARMACEUTICAL COMPOUNDING Lecture 2 - Powders OUTLINE: INTRODUCTION 1. MICROMERITICS 2. COMMINUTION 3. BLENDING POWDERS 4. MEDICATED POWDERS 5. BULK POWDERS 6...

PHMD 1012 1 EXTEMPORANEOUS PHARMACEUTICAL COMPOUNDING Lecture 2 - Powders OUTLINE: INTRODUCTION 1. MICROMERITICS 2. COMMINUTION 3. BLENDING POWDERS 4. MEDICATED POWDERS 5. BULK POWDERS 6. EXAMPLE PRESCRIPTIONS  2 Learning objectives…  3 Introduction- Powders May be amorphous or crystalline Powders: intimate mixtures of finely divided drug or drug and excipient for internal or external use Limited use as dosage form but powders are used to prepare other dose forms Tablets, capsules, suspensions, etc. Amorphous Crystalline This Photo by Unknown Author is licensed under CC BY-NC-ND This Photo by Unknown Author is licensed under CC BY-SA  4 1. Micromeritics: Science of properties of small particles: Particle size, distribution and shape Angle of repose, porosity True and bulk volume Tapped and apparent density  5 Particle size and shape… Small particle size associated with: Larger surface area, faster dissolution, better suspendability Particles of similar shape and size tend to blend more uniformly for more homogeneous mixtures Homogeneity very important for many dose forms  6 Particle size and shape… Particle Size may be determined by:  Sieving methods  Microscopy  Sedimentation rate  Light scattering Particle shape seen by optical microscopy, scanning electron microscopy.  7 Angle of repose… To measure Angle of repose, the powder allowed to flow h tan  The through a funnel and fall freely onto a surface. = height and diameter of the resulting cone are measuredrand the angle of repose calculated by: h tan  = r Where h is the height of the cone and r is the radius of the base. http://pharmatechno2014.blogspot.com/p /d-angle-of-repose.html  8 Angle is a function of size and shape… The lower the angle of repose, the better the flow properties More spherical and smooth particles also result in better flow Poor flow with high rugosity. Rugosity refers to irregular shape and roughness of powder Poor flow with crystalloid needles or plates Poor flow angles >50°  9 Problems seen with poor flow…. https://kemutecusa.blogspot.com/2017/06 /the-problem-of-promoting-flow-from_1.html  10 Particle size vs Particle shape Two different samples with same particle size distributions. Likely that these would behave differently during processing. Flow properties would be dramatically different. Particle size data alone would not allow differentiation between them. Crompton, C PMPS Spring 2005 Particle Shape: An Important Parameter in Pharmaceutical Manufacturing  11 Problems seen with poor flow…. Poor flow led to poor mixing of tablet components (Green areas are drug particles) Non-homogeneous and failed content uniformity test Courtesy Renishaw Ramon Spectroscopy API green and Starch magenta  12 Porosity: True vs Bulk volume Porosity is the percentage void space in the bulk of a powder. Void volume can be calculated from the true volume of the substance and the bulk volume of the powder. Porosity (ε) is the void multiplied by 100 and is a characteristic of a given powder. The values can range from 10 to 90%. Vbulk - Vtrue Vtrue Void = = 1− Vbulk Vbulk W/ true  bulk Void = 1 - = 1− W/ bulk  true  13 Apparent density…. True density is the weight per unit volume For solids apparent and tapped density affected by particle size and shape Larger rougher particles have more spaces between them and an apparent larger volume per unit of mass Implications for dose forms like capsules where volume is fixed  14 2. Comminution: Trituration Communition is the process of reducing particle size of a solid Can be achieved by Trituration with a mortar and pestle  15 Communition: Levigation With spatula Use compatible levigating agent and prepare solid for incorporation into a semi-solid vehicle Small particle size makes product smooth to apply rather than gritty With mortar and pestle Useful technique for preparing suspensions Small particle size to aid in dispersion and suspendability In industry mills are used  16 3. Blending powders: When powders are to be combined into a homogeneous mixture important all the particles are about the same size Powders with different particle size stratify or segregate and do not remain homogeneous Trituration may simultaneously reduce and make size uniform  17 Materials tending to form eutectic mixtures… Acetaminophen Chloral hydrate Prilocaine Aminopyrine Lidocaine Resorcinol Aspirin Menthol Salicylic acid Benzocaine Phenol Thymol Camphor Phenylsalicylate Urea  18 Dealing with eutectic mixtures… Two strategies: 1. Allow eutectic to form while triturating Add an adsorbing inert material until mix is powder- like Use Ca or Mg carbonate or oxide, talc 2. Mix the components separately with adsorbent Combine the protected materials Add remaining materials using geometric dilution  19 4. Medicated powders Powder is a drug or mixture in the solid state May be only drug or drug mixed with excipient Exist as fine uniform particles in homogeneous mixture excipients  20 Medicated powders… Powders may be designed for external use Dusting powder Powder for dissolution followed by soaking or application Powders may be designed for internal use May be incorporated into tablets, capsules or powder papers May also be in bulk for internal use (Metamucil)  21 Medicated powders… Variety of containers are available for topical powders depending on the application  22 Medicated powders… Solid state offers some advantages: Increased stability Most drugs more stable in solid state Flexible Dose forms such as tablet allows controlled release Each dose form can contain different amounts of drug Convenient Solid forms usually easily administered Easy to package and ship  23 Bulk powders… Oral Non-potent medications which can be Metamucil Smooth Texture, Berry Burst Sugar Free Powder - 114 Doses dosed with acceptable accuracy using teaspoons or tablespoons Orally administered powders usually dietary supplements, antacids, laxatives Usually mixed into juice or water prior to oral administration  24 Bulk powders… External Bulk powders for external use dusted onto skin using a sift-top container Often contain an active such as a topical fungicide and a diluent or vehicle powder Diluents should be inert, free of grittiness protects skin and absorbs secretions eg bentonite, talc, kaolin Must have ‘For external use’ auxiliary label  25 Bulk powders… External Bulk powder for topical use Micatin (Miconazole) and Tinactin (Tolnaftate)  26 Powders… Metered doses for inhalation Some powders intended for insufflation into body cavities These are now packaged in aerosol containers under pressure Some are designed to deliver medication directly to the lung  27 A Aerolizer B Handihaler C Flexhaler D Diskus E Twisthaler With these devices, the patient inhales the medication in the form of a fine powder rather than an aerosol.  28 Divided powders… Extemporaneous dose form useful for medications for young children or the elderly Single dose of powdered medication wrapped in paper or foil-plastic laminates Delivers an accurate quantity of medication and can be used for potent drugs  29 Divided powders… Powder consists of active drug uniformly distributed in a soluble diluent like lactose Contents of paper dissolved in water or juice just prior to administration Useful when medication only available as solid oral dose form and patient cannot take  30 Granulations… Granules are coarse particles made by blending powders followed by moistening to form a pasty mass Mass passed through sieve and formed granules are allowed to air-dry Used in preparation of tablets and sometimes capsules Can also be used for non-potent drugs as a bulk preparation where teaspoon or tablespoon used to measure and product dissolved/dispersed in water or juice  31 Granulations… Effervescent granules can be made by mixing granules made with citric and tartaric acids (1:2) with granules made with sodium bicarbonate. More common to see pressed into an effervescent tablet like Alka-Seltzer  32 6. Example Prescriptions Bulk powder – Antacid Dusting powder – Antifungal Powder paper - Antineoplastic  33 Case 1: Paige Turner is a 60 kg, 155 cm tall, 63-year-old woman. She is in good general health and her medication profile record shows that she takes estradiol 2 mg daily for postmenopausal vasomotor symptoms (“hot flashes” and “night sweats”) and omeprazole 20 mg at bedtime for gastrointestinal reflux disorder (GERD). She usually takes an oral liquid combination antacid product after each meal for gastric symptoms, but she is taking a trip abroad and wants a more “packable” powder that she can mix with water and take as needed while traveling.  PHYSICIANS GROUP PRACTICE 34 2756 Main Street Winnipeg MB R2G 6H8 Tel (204) 555-2479 Name: Paige Turner ℞ 123005 Address: 713 Reid Street Date: ℞ Aluminum hydroxide Magnesium hydroxide aa 37.5 g Peppermint oil qs Calcium carbonate qs ad 150 g m ft: 150 g Sig: one level tsp in water tid pc prn Refills: 2 Warren Peace MD.  35 Ingredient function… Aluminum hydroxide Antacid Magnesium hydroxide Antacid Peppermint oil Flavor, scent Calcium carbonate Antacid  36 Formula: Aluminum hydroxide 37.5 g Magnesium hydroxide 37.5 g Peppermint oil 20 drops Calcium carbonate 75 g (150 - 75 g = 75 g)  37 Procedure… Weigh 37.5 g each of magnesium hydroxide and aluminum hydroxide and 75 g of calcium carbonate. Place the magnesium and aluminum hydroxides in 500 mL wide mouth jar. Mix the powders by tumbling until well mixed (about 2 minutes). Add the calcium carbonate and again mix well by tumbling. Add 20 drops of peppermint oil to the powder, distributing the oil droplets as evenly as possible throughout the powder mass. Mix well by tumbling. Remove the cap from a 50 mL wide-mouth pharmaceutical round bottle and use a powder funnel to transfer the powder into the bottle; reweigh and record the weight of the powder. Replace the cap and close securely. Label the preparation appropriately and dispense.  38 Case 2: Gene Poole is a 75 kg, 16-year-old male high school student. A month ago, he joined the swim team at his community pool and soon began to notice intense itching of his feet. His doctor has diagnosed tinea pedis (athlete's foot) and has advised him to purchase over- the-counter (OTC) miconazole cream and to use that with the compounded foot powder prescribed here. Gene's medication record shows that he has no recent or current prescription medications but has in the past used antibiotics to treat occasional infections such as strep throat and sinusitis. He reports that the only OTC medicines that he uses are ibuprofen for occasional muscle strains and a daily multivitamin with minerals. PHYSICIANS GROUP PRACTICE 39 2756 Main Street Winnipeg MB R2G6H8 Tel (204) 555-2479 Name: Gene Poole ℞ 123006 Address: 532 University Cres Date: ℞ Benzocaine 0.75 g Salicylic acid 0.75 g Benzoic acid 1.5 g Camphor 1.0 g Methyl salicylate qs Talc qs ad 30 g m: 30 g Sig: Apply to feet ut dict qAM et hs Refills: 3 Lynn Guinee MD.  40 Ingredient function… Benzocaine Local anesthetic Salicylic acid Keratolytic Benzoic acid Antifungal agent Camphor Antipruretic Methyl salicylate Scent Talc Adsorbent, vehicle  41 Formula… Benzocaine 0.75 g Salicylic acid 0.75 g Benzoic acid 1.5 g Camphor 1.0 g Talc 26 g (30 - 4 g = 26 g)  42 Procedure… Weigh 0.75 g of benzocaine and 0.75 g of salicylic acid, 1.5 g of benzoic acid, 1 g of camphor, and 26 g of talc. Transfer the benzocaine, salicylic acid, benzoic acid, and camphor to a glass mortar and triturate “forcing” the eutectic mixture. Add the talc to the mortar in portions with trituration, adsorbing the liquid eutectic on the talc. Add 6 drops of methyl salicylate drop-wise to the powder with trituration. Pass the powder through the 100-mesh sieve. Weigh the preparation container. Using a powder funnel, transfer the powder to the container and reweigh to determine the final weight of powder. Label and dispense.  43 Case 3: Leah Tarde is a 3-year-old girl who was diagnosed with acute lymphoblastic leukemia (ALL). She has completed the 4-week induction chemotherapy regimen of prednisone, vincristine, and asparaginase and has also received intrathecal therapy (IT) with methotrexate, hydrocortisone, and cytarabine for CNS prophylaxis. Nausea and vomiting were adequately controlled by using intravenous (IV) ondansetron prior to and 4 hours after each IT treatment. She weighs 14 kg and is 91.5 cm tall but cannot swallow tablets, so Dr. Flay indicated that the pharmacy could prepare individual packets of powdered medicine for Leah and it can be given by mixing the contents of a packet with a soft food such as pudding, applesauce, or whipped topping.  PHYSICIANS GROUP PRACTICE 44 2756 Main Street Winnipeg MB R2G 6H8 Tel (204) 555-2479 Name: Leah Tarde ℞ 123007 Address: 725 Charles Street Date: ℞ Mercaptopurine 75 mg/m2/day m et ft divided oral powders #14 Sig: Give contents of one packet with breakfast and supper Refills: 1 Sue Flay MD.  45 Ingredient function… Mercaptopurine Antineoplastic (API) Lactose Diluent, filler API – Active pharmaceutical ingredient Will use commercial 50 mg tablets as source of API  46 Calculations… Calculate Px area use Mosteller equation: Ht(cm) x Wt(kg) 91.5 x 14 SA(m 2 ) = = 0.5965 m 2 3600 3600 Daily Dose: 75 mg/m2 x 0.6 = 45 mg mercaptopurine (MP) Therefore: Each dose is 45/2 or 22.5 mg mercaptopurine.  47 Calculations… Need 15 doses? so need 15 x 22.5 mg = 337.5 mg MP One tablet contains 50 mg MP and weighs 283 mg Need 337.5/50 = 6.75 tablets so take 7 tablets and crush Total weight = 7 x 283 mg = 1981 mg tablet material Need 6.75 x 283 mg = 1910 mg Discard 1981 – 1910 = 71 mg?  48 Calculations… Each powder paper 300 mg? Need 15 x 300 = 4500 mg total Have 1910 mg tablet material so… will need 4500 – 1910 = 2590 mg of lactose as filler.