Quality Control Tests for Tablet Dosage Forms PDF

Dr Javed Qureshi Quality control Tests for Tablet Dosage forms Learning objectives 1. To learn various official and unofficial quality control tests used to evaluate the quality of tablets. 2. To learn the acceptance or rejection of a batch of tablets on the basis of quality control acceptance...

Dr Javed Qureshi Quality control Tests for Tablet Dosage forms Learning objectives 1. To learn various official and unofficial quality control tests used to evaluate the quality of tablets. 2. To learn the acceptance or rejection of a batch of tablets on the basis of quality control acceptance criteria. 3. To understand the importance of each test in evaluation of tablets. 4. To know and learn the working of instruments and equipment used to evaluate tablets 2 Tablet evaluation Unofficial tests Official Tests Identification Tests Appearance Thickness and Diameter Friability Test Disintegration Test Hardness organoleptic properties Weight Variation Test Uniformity of Dosage Unit Test Dissolution Test Assay Test Specific Pharmacopoeial Tests of Tablets • • • • Microbiological Examination of Tablets Acid-Neutralizing Capacity Quality test of Splitting Tablets with Functional Scoring Water content Appearance The appearance of a tablet includes the measurement of a number of attributes such as a tablet’s shape, surface texture, diameter, thickness, color, absence or presence of an odor, taste, physical flaws and consistency, scoreline, and any unique identification markings such as embossed or engraved with a logo or letter(s). Unique Identification Markings Pharmaceutical companies often use some type of unique markings such as embossed or engraved with a symbol or letters or printing on the tablet for rapid identification. The tablets may score in halves or quadrants to facilitate breaking or to make the smaller dose. Intact and clear unique identification markings on tablets are acceptable. Tablet thickness Tablet thickness is important for tablet in reproducing tablet identical in appearance but also to ensure that every lot can be packed in selected packaging components. The thickness of the tablet may be measured manually or by automatic equipment. ± 5% variation is allowed depending on the size of tablet. 7 Thickness Thickness can vary without change in weight due to: ▪ ▪ ▪ ▪ ▪ Diameter of the die the amount of fill permitted to enter the die Difference in the density of granules The pressure applied on the tablets The speed of the tablet compression. Hardness ( Mechanical strength of tablets) Crushing strength It is the load required to crush the tablet when placed on its edge. (diametrically) 9 Why do we measure hardness? 1. 2. 3. 4. To determine the need for pressure adjustments on the tableting machine. To withstand the mechanical shocks of manufacturing, packaging, and shipping, To ensure consumer acceptance. Resistance of tablet to Chipping, abrasion or breakage during storage, transportation and handling before usage depends on hardness. Effect of hardness of tablet Hardness can affect the disintegration. • if the tablet is too hard, it may not disintegrate in the required period of time. • if the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or packaging Factors affecting hardness of a tablet ? Compression of the tablet and compressive force. Amount of binder. (More binder à more hardness) • Method of granulation in preparing the tablet • wet granulation method gives more hardness than direct method, Slugging method gives the best hardness). • Certain tablets such as lozenges and buccal tablets are intended to dissolve slowly intentionally are made hard; others such as immediate-release tablets are made soft. 12 Limits: Oral tablets have a hardness of 4 to 8 Kg; hypodermic and chewable tablets have a hardness of 3 kg sustained release tablets have about 10-20 kg. Apparatus: 1. 2. 3. 4. 5. Monsanto, Schleuniger, Erweka, CT 40, Pfizer, Strong Cobb 14 Factors affecting hardness Moisture content Amount of lubricant Particle size and shape: Too coarse or Too fine Moisture content • A small proportion of Moisture content is desirable for the formation of a coherent Tablet. • The amount of moisture present on the Powder surface is just sufficient to fill the remaining voids in the bed. • Further increase in Compression force results in this water being squeeze out to the surface of Tablet. • This expelled Moisture may act as a lubricant at die wall, but It causes material to stick to punch forces. Effect of moisture on tablet hardness At low moisture content there will be increase in die wall friction due to increased stress, hence the Tablet hardness will be poor. At high moisture level the die wall friction is reduced owing to lubricating effect of moisture. At further increase in moisture content there will be decrease in Compact strength due to reduction in Interparticulate bond. Lubrication Lubricants are commonly included in Tablet formulations in order to reduce: • Die wall friction. • To improve flow properties & Antiadherant properties. However, their presence may cause undesirable changes in Tablet properties. Effect of Lubrication on Tablet Strength Shotton & Lewis investigated the effect of Mg. Stearate on the strength of Tablet of crystalline materials & two simple granulation without binders. They found that Lubricant decrease the strength of all Tablets. The softening of Tablet by lubricants has been reported by Strickland who observed that Mg. Stearate & other Lubricants added as dry powder to granules, They appeared to adhere & form a coat around individual granules. Reference: Lewis, C.J., and Shotton, E. (1965) J. Pharm. Pharmac. 117 supp1. 82s-86s. • Bolhuir showed that Mg. Stearate forms an adsorbed lubricant film around host particles during the mixing process. • The Lubricant film interfere with the bonding properties of host particle by acting as a physical barrier. • This can be seen when the Tablet crushing strength is plotted as a function of the Log of the mixing time with the Lubricant. Bolhuis, G.K., Lerk, C.F., Zij1stra, H.T., andDe Boer, A.H (1975), Pharm. Weekb1ad. 110 317-325. Effect of lubrication on Tablet strength The decrease in strength with an increased mixing time of Tablet ingredients with Lubricants is caused by the formation of this Lubricant film, which interfere with the binding of the particles. The decrease in crushing strength has been attributed to weaker bonds after compression between Lubricant – Lubricant molecules rather than strong excipient bonds. Effect of particle size on tablet hardness • The size of a particle is a complex characteristic and its importance in relation to powder properties is therefore difficult to assess. • Generally, particles with optimum size will give good strength for tablets. • Smaller particles have larger surface area &when these are expose to atmosphere may prone to oxidation, moisture adsorption take place which effect the strength of tablet. • Very large particles often exist as agglomerates of a small crystals on compression these agglomerates breakdown into small units. Friability • It is the tendency of tablets to powder, chip, or fragment and this can affect the elegance appearance, consumer acceptance of the tablet, and also add to tablet’s weight variation or content uniformity problems. • It is related to hardness. 23 FRIABILATOR An instrument called friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging, handling, and shipping. Friabilator determine friability by allowing the tablet to roll and fall 6 inches within a rotating tumbling apparatus. Friability 20 tablets are subjected to abrasion and shock by utilizing a plastic chamber that revolves at 25 rpm, dropping the tablets a distance of 6 inches with each revolution After 100 rotations or 4 min the tablets are weighed and the loss in weight indicates the ability of the tablets to withstand this type of wear Friability (% loss) must be ≤ 1% Procedure 1. Weigh 20 tab altogether 2. Put these tablets in the friabilator and adjust the instrument at 100 rpm (i.e. = 25 rpm for 4 min) 3. Weigh the 20 tablets (only the intact ones) F = 100 × (1-w/w0) Where: w0 = weight of tablets before friability w = weight of tablets after friability 4. Friability (% loss) = It must be less than or equal to1% but some chewable tablets and most effervescent tablets are highly friable and require special unit packaging 26 Shipping test • Method to evaluate a new product. • Send package to distant points and back using various methods of transportation. • Condition upon return indicates its ability to withstand transportation handling. 27 Official standards (Q. C. tests) for tablets (Compendial tests) • British Pharmacopoeia (B.P.) & • US Pharmacopoeia (USP) 28 Official tests and specifications for QC and QA of tablets Property Uniformity of dosage form Drug release Test Specification Weight variation Thickness Content Uniformity of weight ± 5% is allowed USP test is done to establish homogeneity of a batch by assaying 10 tablets , RSD calculated which should be less than 6% For compressed uncoated tablets testing fluid is water at 370C. For uncoated tabs- 30 min Coated up to 2 hrs, sublingual tabs 3 min This specification state that a certain percentage of drug must dissolve in a specified time because drug absorption, physiological bioavailability depend on dissolution. Disintegration Dissolution 29 1- Uniformity of active ingredient: WHY? • Traditionally, dose variation between tablets is tested by two separate tests; 1 Weight uniformity 2 Content uniformity • If the drug forms greater part of the tablet, any variation in the tablet weight obviously indicates a variation in the active ingredient. (Weight uniformity test) 30 Weight variation or Uniformity of weight test 1. Weigh 20 tablet selected at random, individually. 2. Determine the average weight. Limits according to U.S.P: 31 Limits ⦿ Upper limit = average weight + (average weight * %error) ⦿ Lower limit = average weight - (average weight * %error) ⦿ The individual weights are compared with the upper and lower limits. Not more than two of the tablets differ from the average weight by more than the % error listed, and no tablet differs by more than double that %. Tablets that are coated are exempt from these requirements but must conform to the test for content uniformity if it is applicable. Weight uniformity ; B.P. design: Weigh 20 tablets individually (i.e. determine the weight of each tablet alone; X1, X2, X3… X20) Average weight of tablets (X) = (X1+X2 +X3+…+ X20)/20 Not more than two of the individual weights deviate from the average weight (X) by more than the % deviation shown in the table below and none deviates by more than twice that %: 33 • Example for Weight uniformity test (B.P.): • Weigh 20 tablets individually (X1, X2, X3… X20) For example; • (200, 202, 190, 205, 201, 200, 198, 190, 199, 203, 210, 220, 210, 201, 202,199, 190, 195, 200, 200 mg) • -Calculate the average weight of tablets • -Average weight of tablets (X) = (200+202+190+ 205+201+200+198+190+199+ 203+210+220+210+ • 201+202+ 199+ 190+195+200+200)/20 = 201.75 mg 34 %Error for a tablet= Difference between Actual tablet weight & Average tablet weight x 100 Average tablet weight % error for tablet 1= 201.75 - 200/201.75 x 100= 0.86% % error for tablet 2= 202 - 201.75/201.75 x 100= 0.12% % error for tablet 3= 201.75 - 190/201.75 x 100= 5.82% % error for tablet 4= 205 - 201.75/201.75 x 100= 1.61% % error for tablet 5= …………… Calculate %error for each tablet 35 Test result: Only one tablet (tablet number 12) deviated >7.5%, and this deviation (%error 9.04 %) is less than 15 %, i.e. tablets passed this test successfully 36 Example 2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Average wt of 20 tab= 125mg Therefore, limit is ±10% of Av wt = +10% and -10% i.e. upper limit 100+10= 110 % Lower limit 100-10= 90% Now calculate 10% of 125= 125x110/100=12.5 Add 12.5 to 125= 137.5 mg Subtract 12.5 from 125= 112.5mg 38 Acceptable range 90-110% 80 90 18/20 tablets- pass 110 120 18/20 should be in this range (means 2 tablets can be outside this range) …………112.5------------------------------------ 137.5 mg……… Double of permissible limit ie. 10%is 20 So no tablets should be outside 80%-------120%, if any, reject the batch 39 Acceptable range 90-110% 80 90 2 3 4 5 110 120 6 12 13 14 15 16 7 8 9 10 17 18 19 20 1 11 40 Acceptable range 90-110% 80 90 16 2 3 4 5 12 13 14 15 7 8 9 10 17 18 19 20 1 11 110 120 6 41 Acceptable range 90-110% 80 90 2 3 4 5 7 110 120 6 12 13 14 15 16 17 8 9 10 18 19 20 1 11 42 Acceptable range 90-110% 80 16 90 2 3 4 5 110 120 6 12 13 14 15 7 8 9 10 17 18 19 20 1 11 43 Acceptable range 90-110% 80 90 2 3 4 5 110 120 6 12 13 14 15 7 8 9 10 17 18 19 20 16 1 11 44 • Example; If Average weight of tablets is 100 mg • As per USP what are limits; • ± 10 (90----110) • 2nd limit- ± 20% i.e. 80-120 mg • BP= ± 7.5 (92.5---------107.5) • 2nd limit ± 15% i.e. 85---115 mg 45 Content uniformity • If the drug is potent (USP specifies 50 mg of the active ingredient or less), the excipients form the greater part of the tablet weight and the correlation between the tablet weight and amount of the active ingredient can be poor, in this case another test (Content uniformity) must be performed. 46 Content uniformity USP defines content uniformity test for tablets containing 50 mg or less of drug substance in case of uncoated tablets and for all sugar-coated tablets regardless to the drug content. • USP design: • Ten tablets are individually assayed, and mean content and RSD calculated (as per method described in the individual monograph). 47 Procedure • Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if 9 of the 10 tablets must contain not less than 85% and not more than 115% of the labeled drug content and the 10th tablet may not contain less than 75% and more than 125% of the labeled content. • If these conditions are not met, remaining 20 tablet assayed individually and none may fall out side of the 85 to 115% range. • it is required for all coated and uncoated tablets containing less than 50 mg of an active ingredient comprising less than 50% of the weight of one dosage unit. • Nine of 10 must contain labeled amount ± 15% and none exceed ± 25% . • If 1 tab is outside 85-115% (± 15%)of claimed content but with in 75-125% (± 25%) or RSD is greater than 6% or both, another 20 tabs are assayed. RSD <6% Acceptable range (±15%) 85-115% 75 85 1 6 2 3 4 5 7 8 9 10 115 125 PASS 49 RSD <6% Acceptable range (±15%) 85-115% 75 85 1 2 3 4 5 115 125 10 6 7 8 9 REPEAT TEST ON ADDITIONAL 20 TABS 50 RSD >6% Acceptable range (±15%) 85-115% 75 85 1 6 2 3 4 5 7 8 9 10 115 125 REPEAT TEST ON ADDITIONAL 20 TABS 51 RSD >6% Acceptable range (±15%) 85-115% 75 85 6 1 2 3 4 5 7 8 9 10 115 125 REPEAT TEST ON ADDITIONAL 20 TABS 52 • Not more than two tablet should be outside 85-115%, One may be present, but an RSD of not greater than 7.8% is now permitted. RSD <7.8% Acceptable range (±15%) 85-115% 75 85 6 1 2 3 4 5 9 3 1 7 8 1 0 4 5 7 1 2 3 4 5 9 1 7 8 1 0 4 5 1 0 115 125 1 0 1 0 29/30 Tab must be in range PASS 53 Disintegration test • It is the time required for the tablet to break into particles. particles are those that will pass through 10-mesh screen. • Liquids used in disintegration: • Water • Simulated gastric fluid (PH = 1.2 HCl) Simulated intestinal fluid (pH =7.5, KH 2PO 4 (phosphate buffer) + pencreatin enzyme +NaOH) 54 Disintegration Apparatus The Disintegration apparatus consists of a basket rack holding six plastic tubes, open at the top and bottom; the bottom of the tubes is covered with 10-mesh screen The basket rack is immersed in a bath of suitable liquid, held at 37°, preferably in a 1 -L beaker. The rack moves up and down in the fluid at a specified rate. For compressed uncoated tablets the testing fluid is usually water at 37°, but in some cases the monographs direct that simulated gastric fluid be used 28-32 cycles/min 50-60 mm Not applicable for sustained release preparations 56 Disintegration Test For most uncoated tablets the period is not more than 30 minutes according to USP ( to BP 15 minutes), although the time for some uncoated tablets varies greatly, from this. For coated tablets up to 2 hours may be required, while for sublingual tablets, the disintegration time is 3 minutes. The tablet disintegration test is limited to manufacturing control of variations in individual products and is not a measure of bioavailability. lot-to-lot It is used to provide a simple and useful means for monitoring and controlling the quality of tablets USP test for uncoated tablet • Start the disintegration test on 6 tablets. • If one or two tablets from the 6 tablets fail to disintegrate completely within 30 min repeat the same test on another 12 tablets. (i.e. the whole test will consume 18 tablets). • Not less than 16 tablets disintegrate completely within the time, if more then two tablets (from the 18)fail to disintegrate, the batch must be rejected. 58 U.S.P. Method for Enteric coated tablets • Put in distilled water for five minutes to dissolve the coat. • Then put in simulated gastric fluid (0.1MHCL) for one hour. • Then put in simulated intestinal fluid for two hours. • If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. • So, 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the batch must be rejected. BP method for Enteric coated tablets: • Put in distilled water for five minutes to dissolve the coat. • Put in simulated gastric fluid for two hours (emptying time). • Put in phosphate buffer (PH 6.8) for one hour. • One or two tablets fail to disintegrate repeat on 12 tablets. So 16 tablets should disintegrate. If more than two tables fail to disintegrate reject the batch. Disintegration test • Test may be modified if tablets are designed not to disintegrate in GIT. • Dispersible tablets must disintegrate in water at 19-21 0C within 3 min. • Effervescent tablets in 200 ml of non agitated cold water at 15-25 0C within 5 min. • Film coated- 30 min • Coated other than film - 60 min in water, if 1 or more fail, repeat in 0.1 N HCl, all tablets should disintegrate. • Enteric coated:1 h in simulated gastric fluid, no sign of disintegration must be seen. 61 Limits: For Uncoated tablets: MEDIUM TEMP TIME LIMIT According to U.S.P. Simulated gastric fluid 37 oC Not exceed 30 min According to B.P. water 37 oC Not exceed 15 min 62 Dissolution test • Dissolution is the process by which a solid enters a solution . • The dissolution rate is defined as the amount of drug substance that goes into solution per time under standardized conditions of liquid / solid interface, temperature, and solvent composition. • Dissolution is one of most important quality control tests and consider as tool for predicating bioavailability, in some cases, replacing clinical studies to determine bioequivalence. • In fact, a direct relationship between in vitro dissolution rate of many drugs and their bioavailability has been demonstrated and is generally referred as in vitro- in vivo correlation (IVIVC). Dissolution test A variety of designs of apparatus for dissolution testing is varying from simple beaker to complex system where an attempt is made to mimic the biological media. The choice of the apparatus to be used depends largely on the physicochemical properties of the dosage form. Dissolution Apparatus Apparatus Name Drug Product Apparatus 1 Rotating basket Tablets Apparatus 2 Paddle Tablets, capsules, modified drug products, suspensions Apparatus 3 Reciprocating cylinder Extended-release drug products Apparatus 4 Flow cell Drug products containing low-water-soluble drugs Apparatus 5 Paddle over disk Transdermal drug products Apparatus 6 Cylinder Transdermal drug products Apparatus 7 Reciprocating disk Transdermal drug products Rotating bottle (Non-USP-NF) Extended-release drug products (beads) Diffusion cell (Franz) (Non-USP-NF) Ointments, creams, transdermal drug products *Apparatus 1–7 refer to compendial dissolution apparatus in USP-NF (United States Pharmacopeia) Scope of Dissolution testing • • • • • Product optimization Monitoring manufacturing processes (PD) In vitro –in vivo correlation (BE studies) Regulatory requirements Dissolution testing should be carried out under physiological conditions • The volume of dissolution medium is generally 500, 900 or 1000 ml • An aqueous medium with a pH range of 1.2 to 6.8 is used 66 Rotating Basket Apparatus -1 In case of none-disintegrating dosage forms this apparatus is superior to apparatus 2 since it constraints the dosage form in a steady state fluid flow It is inferior for testing dosage forms which contains gums due to clogging of screen matrix ROTATING PADDLE (APPARATUS -2) This apparatus is identical to apparatus 1 except that the paddle is substituted for the rotating basket Frequently used for both disintegrating and non- disintegrating dosage forms RECIPROCATING CYLINDER (APPARATUS -3) https://www.youtube.com/watch?v=L8rNcV_qORI RECIPROCATING CYLINDER (APPARAUTS -3) One advantage of the reciprocating cylinder is that the gastrointestinal tract conditions can be easily simulated, as it is easy to make time dependent pH changes This apparatus is most suitable for non disintegrating (extended release) or delayed release (enteric coated) dosage forms FLOW CELL (APPARATUS -4) The advantage of flow through cell apparatus is the ability to test drugs of very low aqueous solubility and the ability to change the pH conveniently during the test https://www.youtube.com/watch?v=XNuVuuLx30c Types of flow in flow through cell There are 2 types of hydrodynamic flow within a flow-through cell viz. a laminar flow and turbulent flow. Laminar flow is achieved by filling the flow-through cell with a 5 mm ruby bead bottom of the cell followed by a layer of 1 mm glass beads. The laminar flow is more controlled as it crosses the dosage form in unidirectional flow. The turbulent type of flow is obtained by placing only the ruby bead in the flow-through cell. The turbulent flow is more beneficial for dosage forms that require a higher agitation rate to release its actives. The open-loop configuration is especially useful for lowsolubility drugs as it can easily provide an infinite sink condition by maintaining a continuous flow of fresh dissolution medium. Dissolution results obtained from the open system are typically expressed as the instantaneous drug concentration, while results from closed systems are usually expressed as the cumulative amount of drug dissolved in the medium (or a percentage of the total amount in the tablet). Closed loop system is useful for very low dosage strength. WHY CHOSE APPARATUS 4? 1. USP apparatus 4 is the ideal choice for poorly soluble drugs 2. USP apparatus 4 is the best method of choice for large media volume dissolution, in order to achieve infinite sink condition 3. For IVIVC studies, automated media changeovers can be easily achieved for solid as well liquid dosage forms 4. Many challenges such as tablet floating, sticking etc. are eliminated PADDLE OVER DISK ( APPARATUS -5) This uses the paddle apparatus 2 with the sample usually a transdermal delivery system, being attached to a stainless steel disk, which is then placed at the bottom of the vessel, directly under the paddle CYLINDER APPARATUS-6 The cylinder method (Apparatus 6) for testing transdermal preparation is modified from the basket method (Apparatus 1). In place of the basket, a stainless steel cylinder is used to hold the sample. The patch is generally attached to a piece of Cuprophan (a dialysis membrane material like cellulose acetate) and glued to the outside of the cylinder. RECIPROCATING DISK METHOD (APPARATUS -7) In the reciprocating disk method for testing transdermal products, a motor drive assembly (Apparatus 7) is used to reciprocate the system vertically, and the samples are placed on disk-shaped holders using cuprophan supports. There are several variants to this apparatus, which is based on a sample holder that oscillates up and down in the medium vessel. Sample holder may take the form of a disc, cylinder, or a spring at the end of a stainless steel or acrylic rod. The sample is attached to the outside of the sample holder either by virtue of being self-adhesive or is glued in place using a suitable adhesive Method of dissolution testing • In the general procedure for dissolution test, a liquid named as dissolution medium is placed in the vessels of a dissolution unit. The dissolution medium should be water or water-based having a pH in the range of 5-7 at 37 ºC. Medium should be used according to the standard test procedure of the product. • The dissolution medium should be degassed through sonication method as the presence of dissolved gases could affect the results. This is why the drug is placed within the medium in the vessels once it has reached sufficient temperature. • HPLC and Ultra Violet visible spectroscopy detects the sample solutions. • The tested samples must meet the criteria of release specifications. The parameter “Q” denotes the percentage value of quantity of active ingredients dissolved within the monograph of a sample solution. Dissolution limits All 6 tablets must meet the requirements specific. If one or two tablets failed, repeat the test on 6 additional tablets. If the initial sample analysis, known as S1 or stage 1 testing fails to meet the acceptable value for Q, then additional testing known as stage 2 and 3 testing is required. S3 testing is performed only if S2 testing still fails the Q parameter. If there is a deviation from the acceptable Q values at S3, then an OOS (Out of Specification) investigation is generally initiated. S1 = Each Unit should be Q+5%. S2 = Each unit should be equal to or more than the Q value and no unit is less than Q15%. S3 =Each unit should be more than Q, Not more than 2 units are less than Q-15% and No unit is less than Q-25%. Factors affecting the dissolution of a tablet • The particle size of the substance • The solubility and hygroscopicity of the formulation. • The type and concentration of the disintegrant, binder and lubricant used • The manufacturing method • Compactness and the force of compression used “Various pharmacopoeias contain specifications on dissolution requirements of various drugs. ( monograph specifies : stirring speed, temperature, viscosity, pH, composition of dissolution media and presence or absence of wetting agent) " • B.P.: • Acidic media are used with basic drugs Eg. 0.1 M HCl with Quinine Sulphate • More alkaline media with acidic drugs Exp. pH 6.8 buffer with phenoxy methyl penicillin • Water for non ionizing molecules such as digoxin • Sample is removed from dissolution fluid after 45 min and analyzed. • The most common standard is that 70% of stated amount of drug must be in solution after this time has elapsed. 88 Microbiological Examination of Tablets (Nonsterile Products) This test is used to determine the absence or limited occurrence of specified microorganisms that may be detected under the conditions described. Some liquid oral products can be subject to extreme microbiological control, and others require none. Generally, the microbial content test should not require for most of the tablets except vitamin tablets, and sugar-containing tablets. It is a crucial pharmacopeial test for the evaluation of tablets or quality control tests of tablets. Acceptance Criteria for Microbiological Quality of Nonsterile Dosage Forms ROUTE OF ADMINISTRATION Non-aqueous preparations for oral use TOTAL AEROBIC MICROBIAL COUNT (CFU/G OR CFU/ML) 103 TOTAL COMBINED YEASTS/MOLDS COUNT (CFU/G OR CFU/ML 102 SPECIFIED MICROORGANISM(S) Absence of Escherichia coli (1 g or 1 mL) Acid-Neutralizing Capacity Acid-Neutralizing Capacity is a pharmacopoeial test for the evaluation of tablets or quality control tests of tablets. Certainly, this test is applicable only to measure the acidneutralizing capacity of an antacid tablet. The acid-neutralizing capacity (ANC) is the amount of acid that can be neutralized by an antacid. The United States Pharmacopoeia (USP) describes the ANC test as a back-titration method using sodium hydroxide (0.5N solution) to a set endpoint of pH 3.5 to determine the number of milliequivalents of acid (hydrochloric acid 1N solution) neutralized by the minimum labeled dosage (MLD) of an antacid Scored Tablet SPLITTING OF TABLET Guidelines and criteria for scored tablet evaluation The dosage amount meant to be achieved after splitting the tablet should not be below the minimum therapeutic dose indicated on the approved labeling. The split tablet should be safe to handle and not pose risk of unintended drug exposure. The split tablet portions should meet the same finished-product testing requirements as for a whole-tablet product with equivalent strength. An acceptable tablet breaks into the designed number of segments, and each split portion has NLT 75% and NMT 125% of the expected weight of the split tablet portion. NLT 28 of the 30 tablets is acceptable Quality test of Splitting Tablets with Functional Scoring • • • • All scored tablets should be stable at: 5 °C, 25 °C/60%RH, 40 °C/75%RH for up to 90 days. Stability studies should be performed in appropriate container closures. Scored tablets should be stable in pharmacy dispensing containers (no seal/no desiccant), for up to 90 days 25 °C/60%RH. The label should encompass the therapeutic dose. Enteric coated tablets should not be scored. Water content determination The water content of tablets before and after stability study at specified temperatures and humidity for a fixed time may determine to find out moisture impact on tablets. Generally, water content calculated by using the method is Karl Fischer titration. In summary, by using the above quality tests, Quality control analysts may evaluate tablets, and after satisfactory results, may release a manufacturing batch of tablets