Uy, Alyssa V.

2BPh CHAPTER 8 Tablets

Tablets - solid dosage forms usually prepared with the aid of suitable pharmaceutical excipients Majority are administered orally, while others sublingually, buccally or vaginally contain features most applicable to their routes of administration. Types of Tablets: Compressed Tablets (C.T.) - manufactured with tablet machine capable of exerting great pressure or compacting the powdered or granulated tableting material. DILUENTS, BINDERS, DISINTEGRANTS,
ANTIADHERENTS/ GLIDANTS/LUBRICANT, COLORANTS/FLAVORANTS

Effervescent Tablets prepared by compressing granular effervescent salts that release gas when in contact with water. This tablet contains medicinal substance which dissolves rapidly when in contact with water. Molded Tablet Triturate (M.T.T.) small & cylindrical, very soft, soluble & designed to dissolve rapidly. Compressed Tablet Triturate (CTT) prepared by compression (limited pressure) usually containing potent substance. Sucrose and lactose are used for diluent. Hypodermal Tablet (H.T.) used by physicians for extemporaneous preparations of parenterals. It is meant to be dissolved in suitable vehicle, sterility attained, and the injection performed. The advent of prefabricated injectable products and disposable syringes declined its use. Dispensing Tablets (D.T.) or compounding tablets used by pharmacists when compounding prescriptions and not dispensed to patients. It contains large amount of potent subs. enabling the pharmacist to obtain pre-measured amounts. For compounding multiple dosage units. Immediate Release Tablets (I.R.) designed to disintegrate and release their medication and therefore are devoid of special rate controlling features like coating and other ways. Instant Disintegrating/Dissolving Tablets characterized to dissolve within 10 seconds to 1 minute. This is possible with the use of lyophilization techniques, soft direct compression, or the use of water-soluble excipients designed to wick water into the tablet for rapid disintegration. Extended Release Tablet (E.R.) /Controlled Release (C.R.) designed to release their medication in a predetermined manner over an extended period of time. Vaginal Tablet/Inserts uncoated and bullet- or ovoid- shaped tablets for localized effect. Prepared by compression and shaped to fit smugly into plastic inserter devices. They contain antibacterials (against Hemophilia vaginitis) and antifungals (against Candida albicans) The physical features of compressed tablets are varied; its diameter and shapes are determined by the die and punches used in the compression. The less concave the punch, the more flat the resulting tablets. Punches with raised impressions will have recessed impressions on the tablets.

Multiple Compressed Tablets (MCT) prepared by subjecting the fill material to more than a single compression, the core (inner) and shell (outer) Sugar-Coated Tablet (S.C.T.) the coating maybe colored or uncolored sugar layer, water soluble and quickly dissolved after swallowing. Purposes: to protect the enclosed drug from the environment and to provide a barrier to objectionable taste and smell of the drug. Disadvantages: time and expertise needed in the coating process and increased shipping costs Film-Coated Tablets (F.C.T.) coating is made of thin layer of a polymer capable of forming a skin-like usually colored film over the tablet. Polymer is cellulose acetate phthalate. Advantages of film coating over sugar coating: more durable, less bulky and less time consuming to apply. Gelatin Coated Tablet capsule-shaped compressed tablet with 1/3 the size of capsule with the same amount of fill, more ease in swallowing & more tamper evident. (GelCaps) Enteric-Coated Tablets (E.C.T.) have delayed release features, designed to pass the stomach to the intestines where the tablet will disintegrate allowing drug dissolution & absorption. Needed when drug substance: a) b) c) is destroyed by gastric acid is irritating to the gastric mucosa by-passed the stomach enhances the drug absorption in the intestines

Buccal tablets flat, oval tablets intended to be dissolved slowly in the buccal pouch. It is for oral absorption of drugs destroyed by gastric acid or poorly absorbed in the GI tract. Sublingual Tablets designed to erode promptly underneath the tongue for rapid drug effect. Lozenges or troches disc-shaped solid forms containing a medicinal substance in a hard candy or sugar base. Meant to dissolve slowly for localized effect or systemic effect Chewable Tablets have rapid disintegration when chewed or allowed to dissolve in the mouth, have a creamy base usually specially flavored and colored mannitol. Meant for large-sized tablets given to children and adults with difficulty in swallowing solid dosage forms

Quality Standards and Compedial Requirements: USP Weight Variation Test: 10 tablets are individually weighed and average weight calculated. Content Uniformity: Dosage units are assayed individually and requires that each dosage unit is 85% - 115% of the label claim (S.D. is less than 6%) Tablet thickness is determined by a. b. c. d. the diameter of the die the amount of fill the compactibility of the fill material the force of pressure applied during compression.

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Tablet thickness is measured by a hand gauge. Tablet hardness affects its disintegration & drug absorption. The greater the pressure, the harder the tablet. It should be hard enough to resist breaking during the normal handling and yet soft enough to disintegrate properly after swallowing. A force of 4 kilograms as determined by hardness tester is minimum requirement for a satisfactory tablet. Tablet friability the tendency to crumble by allowing it to roll and fall within the rotating machine (friabilator). A maximum weight loss of not more than 1% of the weight of the tablets being tested is acceptable. Tablet Disintegration Test uses a basket-rack assembly containing 6 open ended transparent tubes held vertically upon a 10-mesh stainless steel wire screen. The basket is raised and lowered in the immersion fluid (water at 37oC) at a frequency of 29-32 times per minute. Result: the residue of the tablet on the screen is a soft mass having no palpable inner core. Disintegration time ranged from 2 mins. to 4 hours depending upon the monograph. For enteric coated tablets, test is done in a simulated gastric fluid for 1 hr. No sign of disintegration must be seen. They are immersed in a simulated intestinal fluid for the time stated in the monograph where they disintegrate completely.

are withdrawn for chemical analysis. Samples must meet the requirement stated in the monograph. Pooled dissolution testing samples coming from different batches placed in individual dissolution vessel in the apparatus or multiple dosage units in a single vessel. This recognizes the concept of batch characteristics.

3 methods for compressed tablet: Wet Granulation: Weighing and blending of ingredients (A.I. & adjuvants) + liquid binder screen the damp mass (Sieve 6-8) dry size the granules (Sieve 12-20) + lubricant and blend compress Fillers lactose and microcrystalline cellulose Binder to facilitate adhesion of powder particles. Starch, povidone, methylcellulose. Flavorant and colorant are added to binder. Lubricant to improve the flow of granules from the hopper to the die; prevent adhesion to the punches and die during compression; reduce friction between tablet and dies wall during tablet ejection and provide tablet sheen. Calcium and magnesium stearate are examples. All-In-One Methods: 1) Fluid-bed Process fluid-bed granulator which performs the blending, granulating, drying into 1 continuous process 2) Microwave Vacuum Process powder mix is mixed, wetted, agglomerated and dried using microwave Dry Granulation the powder mixture is compacted to large pieces and broken down or sized into granules Active ingredient or diluent must have cohesive properties. Advantages: For materials that are degraded by moisture or by elevated temperature during drying Steps in Dry Granulation: Weighing & blending powder mix slugging sizing + lubricant compression Tableting machine compress tablet formulation within a steel die cavity by the pressure exerted by the movement of the two steel punches (upper and lower). Imperfections of tablets: a) a)Laminations horizontal striations b) Tablet capping the top of tablet separates from the whole c) Tablet splitting Reasons: a) particles has no time to bond due to fast high speed production b) air is entrapped during direct compression c) punches not clean d) aging

Tablet dissolution test - Uses: guides formulation and product development performance of manufacturing process can be monitored by it (quality assurance) c. Consistent results assure bioequivalence from batch to batch d. As a requirement for regulatory approval Its goal to provide a reasonable prediction or correlation with the products in vivo bioavailability. a) b) c) d) High Solubility and High Permeability IVIVC Low Solubility and High Permeability IVIVC High Solubility and Low Permeability limited IVIVC Low Solubility and Low Permeability none a. b.

In (a) IVIVC is expected if the dissolution time is slower then gastric emptying time (limiting factor). Dissolution Test Apparatus consists of: 1. 2. 3. variable stirrer motor stainless basket on a stirrer shaft (Apparatus I) or a paddle as stirrer (Apparatus II) 1-L vessel glass with a cover having the shaft of the stirrer fitted at the center port, with 3 ports for samples and 1 port for the thermometer Water bath to maintain the temp. of the medium in the vessel

4.

Dissolution medium is placed in the vessel at 37oC + 0.5o C. The stirrer is rotated at speed specified and at stated intervals; samples of the medium

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Direct Compression appropriate for chemicals with flowing and cohesive properties Tablet Deduster to remove traces of loose powder adhering to the tablets following compression. Tablets are coated: 1) to protect from air and/or humidity 2) mask the taste 3) provide characteristics of drug release 4) to provide aesthetics or distinction to the product Sugarcoating tedious, time-consuming and needs expertise of qualified technician and the product doubles the size and wt. Film coating provides a thin, skin-tight coating of a plastic material over the compressed tablet. Components: a) Film former to produce thin smooth film. Cellulose acetate phthalate b) Alloying substance to provide water solubility/ permeability for body fluids to penetrate through and make the drug available. Polyethylene glycol c) Plasticizer to produce elasticity/flexibility to the coating & provide durability. Castor oil Advantages: Size and wt. almost the same as the tablet, more resistant to destruction by abrasion, markings can be embossed on the coating. Enteric coating maybe accomplished through coating with enough thickness or coating which allow dissolution at a pH 4.9 or higher. Example is shellac Fluid Bed or Air Suspension Coating spray coating of powder, pellets, granules or tablets held in suspension by a column of air Depending where the coating solution come from: a) Wurster the bottom of the cylinder b) Top spray sprayed downward c) Tangential spray techniques rotary fluid bed coater Top spray recommended for taste masking, enteric release and barrier film on tablets. Bottom spray for sustained release and enteric release Tangential layering coating, sustained and enteric releases Compression Coating the coating material (granulation or powder form) is compressed into the tablet core. Advantages: a) It is anhydrous process appropriate for drugs affected by moisture

more uniform coating uses less coating material resulting to lighter, smaller and easy to swallow tablets d) less expensive to package and ship Packaging and Storage: a) Use tight, light resistant (amber) containers, if adversely affected by light b) Store in places of low humidity and protected from extreme temperature c) Use desiccant pellet is affected by moisture

b) c)

Oral administration of solid dosage forms Lozenges by compression or molding. Meant to dissolve slowly in the mouth for localized effect. Impact of Changes on Solid dosage forms: 1. Changes in formulation a) active ingredients b) excipients c) their quantities d) addition of new excipients 2. Changes in methods of manufacturing a) new machineries b) different steps in manufacturing c) different in process controls, tests or assay methods d) production of different batch sizes e) use of different product reprocessing procedures f) suse of different manufacturing sites

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