Upon completion of this exercise, you should be able to: ~ +> Describe the advantages and limitations of capsules as dosage forms. * Describe the official USP tests required for capsules. ‘+ Prepare and dispense hard gelatin capsules. Evaluate capsules as a dosage form by performing and analyzing data from official USP tests. Capsules are gelatin shells filled with the ingredients that make up an individual dose. Dry powders, semi-solids, and liquids that do not dissolve gelatin may be encapsulated. FRBE LEIP ELOL A ORL, ® Capsules have several advantages as pharmaceutical dosage forms: soft They may be usec to mask the unpleasant tastes, aromas, or appearance of a drug, ‘98% * They allow powders to be dispensed in an uncompressed form, thus allowing for ASiuicker dissolution and absorption ofthe drug following oral dosing (as compared with tablets). easiely + They offer the pharmacist versitility to prepare any dose desired for a variety of / administration routes (e.g. oral, inhalation, rectal, or to be diluted for vaginal, rectal, oral or topical use). eee Be SEES POSS Nelo. Seats + They may be easier than tablets for some people to swallow. OFS SSR a + They can be make to alter the release rate ofthe drug. —_~_"5- ONS as miseon y Saco eee as @ Their disadvantages or limitations include the following: + They are easily tainpered (although techniques exist for preventing this). Z. « They are subject to the effects of relative humidity and to microbial contamination. Cy + They may be difficult for some people to swallow. ‘+ More expensive (commercially). Mm bee. VAs Solergy os gow Sag “ab 5:; Capsule dosage form \once onei BRNO RMS NI San Tr choice oF Cogidepindoa Sieg a Q Ane syee re teevt den Cawtein. The hard gelatin capsule consists of a base or body and a shorter cap, which fits firmly over the base of the capsule. For human use, eight sizes of capsules are available. The capacity of each size varies according to the combinai ite ak fiorroF drugs and their apparent densities. 0} Capsules are available as clear gelatin capsules or in a variety of colors. we Spee aoe F —p- Some types of hard gelatin capsules have a locking cap, reopen the capsule. SS ‘soi onst s Som which makes it more difficult to caphcitigs of capstiles are given hetow. By kaowing ice oPagfeule steais ustpefly maddsgsier; arfnackst. Mg of Lactose 1340 929 665 489 362 293 195 127 fops the judgrtent bf the begidning Mg of Aspirin 1000 600 500 300. 250 : ot 200 125 60 Ss ae Nols: To hand fill capsules at the prescription counter, the pharmacist generally uses the "punch" method. The Ingredients are triturated to the same particle size and then mixed by geometric dilution. The powder is placed on a powder paper or ointment slab and smoothed with a spatula to a hight approximately half the length of the capsule body. The base of the capsule is held vertically and the open end is repeatedly pushed or “punched” into the powder until the capsule filled; the cap is then replacedto close the capsule. Poe eee oa cero ee eee eter e Tab 5: Copsule dosage formEach filled capsule is weighed using an empty capsule as a counterweight. Powder is added or removed until the correct weight has been placed in the capsule. The filled capsule is tapped 30 that no air spaces are visible within the contents. It is a good practice to remove from the stock container the exact number of empty capsules needed before you begin filling thern. In this way you avoid preparing the wrong number of capsules and at the same time avoid contaminating the empty capsules with drug particles that cling to your hands. Also, since some fill material will likely be lost in the process of punching capsules, the pharmacist generally calculates for the preparation of at ‘east one extra capsule fo Insure enough fill for the Tast capsule, ‘ BS SR SENS we ; i aad sap The simplest Prethod by which a capsule may be kept free of mois ure dus wes Sar choy a (gtowash ihe hands wal, [ dry them, and keep the fingers dry by strippinf'a towel through Seale the cleansed fingers until warmth is felt. An alternative method isto use the base ofone _ *\*e* capsule as a holder for other bases during the filling operation. The capsules do not come in contact: ingers. The most sure method of protecting the capsule is to wear finger cots or rubber gloves. §=©——@)_ cots or rubber gi Capsule machines are available for Pilling 50, 100, and 300 capsules at a¥ime. Each manufacturer's machine is slightly different in its operation, but the series of operations isthe me. core! if Ie eet Capsules age first loaded into the machine. Most machines come with a capsule ‘cadet which correctly aligns all of the capsules in the machine base, There are plates on the machine base that can be adjusted. First, the plates are adjusted to hold the capsule bodies in place while the caps are removed all at one time. The caps remain in place in the top of the machine for later use. Then the plates are adjusted again so that the capsule bodies will "drop" into place so that the tops are flysh with the working surface of the plate. a? oo? ed The formulation powder is poured onto the plate and special spreaders and combs are used to fill the individual capsules. Some manufacturer's have special shakers that will also help spread the powder and fill the capsules. The powder is spread eygoly over the plate, and the comb is used to tamp and pack the powder into the capsules. These two processes are repeated over ‘and over Sgain until the capsule bodies are filled with the powder. All of the caps are then simultaneously returned to the capsule bodies, and the closed capsules are removed from the ay ce ° 1 ews) we dete eaeddd conte be cog-Ut > The machine has the advantage of filling many capsules in a timely manner. However, there is a tendency to pack the capsules in the middle of the plate with more powder than the capsules along the periphery. Ittakes practice to ensure that each capsule has the same amount of drug. ‘quality control procedure should be executed with each batch of capsules produced with the wie “ab 5: Capsule dosage form 3 meistmere 2 How protet Cp. Prom, machine.machine. eT enon we Ue Once the capsules have been compounded and the capsule closed, the pharmacist may want to Barrie capoTe-The best way is to use "locking" capsules, where the body and cp lock ‘together, making It very difficult to open the capsule again. If using locking capsules, during the filling process the cap is not completely closed onto the body in the wel ighing procedure to determine the weight of powder in the capsule. The locking is done only one time and that is |) Fertheapaile scoreaty Me If locking capsules are not used, a seal can be made by touching the outer edge of the body with amgist towel to soften the gelatin. Alternatively, a cotton swab dipped in warm water can be ‘Fubbed around the Inner edge of the cap. When the cap is closed on the body, itis slightly twistedto form the seal. > Capsules should be visually inspected and checked for) ‘7 Uniformity - check capsules for uniformity in appearance and color. %,« Extent of fill - check capsules for uniformity of extent of fill to ensure that all capsules have been filled. ar — 7° locked = check capsules to ensure that they have all been tightly closed and locked. Say. uendran uae Ne Seema Wee Sa Al Seckon <795> of the USP 24/NF19 Supplement 1 requires that the capsule, "shall not be less 4 than 90%and not more than 110%of the theorecally calculated weight of each unit." This "weight variation" requirement (discussed in Seck on <905> of the USP 24/NF19) measures the variability in the amount of powder contained in each capsule. This procedure can be carried out in all pharmacies. ‘The other Dosage Form Uniformity test of SecKon <905> is "content uniformity" which measures the variability in the amount of active drug contained in each capsule. Most pharmacies are not equipped to carry out content uniformity analyses since special analytical equipment is required. - of ood midiny, Sint -quipr a Urey) tee nck aes “yy > Itis possible to have capsules that pass the weight variation requirement but not have content uniformity. This can occur if the material put into the capsules is not a homogenous mixture of TUthe ingredients. Some capsules would then have more acth other capsules. ‘Appropriate mixing (Le,, Baamétrie dilution) of all capsule ingredients into a homogenous Thixture before filling the capsules.Jn this manner, the weight varlation data will be sufficient to ve Weight variation data will be sufficient to _ ensure the quality of the capsule: | SS —— Capsule dosage forma woe = aes Bi ee Capsules are made of gelatsn, sugar, and water and contain about 10%to 15%moisture. Gela¥in can absorb up to ten times its weight in water. So if gelatin capsules are placed in areas of high humidity, they will become malformed ish&pened as they absorb moisture. On the other brand, if capsules are placed in low humidity, they become dry and brittle and may crack. To. protect Capsules from thé extremes of humidity, they id be dispensed in plastic or glass vials and stored ina cool, drug place. it appears that a storage relat ve humidity of S0%to 45%is best. Cotton can be placed in the top of the vial to keep the capsules from rattling. as > |f powders that are being mixed before encapsulation are very light and fluffy and "difficult to manage," adda few drops of | gral ‘water, or mineral oll, As an alternative, mix these powders ina plastic bag. If the powders Seem to have a “static charge," use about 1%sodium lauryl eo ——erreEeEeeEeEeeeeeeeeeeeeee 4 Magnesium stearate (less than 194 can be added to powders to increase their "flowabllity” which makes filling capsules easier. However, magnesium stearate is a hydrophobic compound and may interfere with the dissolution of the powder cog eend Set Conben sa Ne HAs wes eye We quekiy ~\s peter fap \e— ma den ab \ar Cor Poun aad we aeete Shela dle Yleorry ea @ Prk We ca. io pes’ ae Or des Nes) @D sdeare eee Vee dey Sn acl ond ay plac « BD Medan Wowdsly Ghenld be 30-457 @B Se colar ok Mehod of Ma vail le Ree Bre @Q. rom gobbling: and Prevent SL dely eater tee reve PRUE X ‘Capsule dosage formCompound, label, and dispense the following prescription: (PREPARE 10 CAPSULES - / A. Manual Filling of Hard Gelatin Capsules 2 y Dispense six (6) capsules and save four (4) capsules for analysis. Calculate for 11 capsules.) Rx “NS +e Salicylic Acid. | 4.mg ge ot =e > Lactose q.s. 550mg ei 9k? M.Ft.D.T.D. caps #10 | [ Amount of Salicylic Acid Needed for Capsules Preparation of trituration Make the necessary calculations and describe how the trituration will be prepared. Salicylic Acid mg Lactose mg Total Weight of Trituration ma Total Amount of Lactose Needed to Make 10 Capsules of Desirable Weight Total Weight of 10 Capsules ma Capsule Size Needed mg 7" Visual Inspection of Final Preparation e vet B. Evaluation of Capsules i Give the compounding formula | NOTE: Capsule contents should be analyzed in the same order as weighed in the weight variation test so that a comparison between weight variation and content uniformity can be made. i, 1. Weight Variation Using the balance, weigh each capsule, taking care to preserve the identity of each. + Empty the contents of each capsule into a flask and weigh the empty capsule shell. * Determine the weight of t ts of each capsule. . Cala 7 following for theW% of Intended Weight": Lab. ipsule dosage form_ Yok stendel oe Ee Se Sy mare wt f 3AN Inne permeny laberatury manned a Jee ‘ivi 3 ww Capsule # Weight of Weight of Weight of % of Intended Finished Capsule Empty Capsule Contents Weight | 1 | 2 3 3 mean =____ mn wk 2 XY 2. Content Uniformity + To-each flask containing the contents of one capsule, add 100 mi of 0.01. N NaOH. Prepare a blank of 0.01 N NaOH. Using a set of reference standards of known concentration, prepare a Beer's Law plot. Read the absorbance of each standard and sample at 310 nm using the spectrophotometer. Using the slope and intercept of the Beer's Law plot to convert absorbance to concentration, calculate the weight of active ingredient in each capsule. * Calculate the following for the "% of Labelled Claim": the mean standard deviation relative standard deviation Prepare a Beer's Law piot of the following salicylic acid standards. Attach graph. Salicylic Acid Absorbance @ 310 nm Regression Analysis : 0.00.meg/mi intercept = di i 0.2. meg/ml 0.4 mco/ml slope = 0,6 meg/ml eee ee 0.8 meg/ml Rese 1.0 meg/ml if i i ee 7 “Amount in Capsule | % of Labelled Capsule # Absorbance Concentration ee) quiet anwne mean = standard deviation relative standard deviation tab 5:: Copsute dosage form ]