Wn ueae myer changes i and its dosage form. wh a . _ ‘ ml ty of 1 physicochemical properties of the drug “al rat ars DISSOLUTION APPARATUS DESIGN ha hy a dissolltion test, They are : 38 gn, the size of the container, ision ral factors that must be considered in the design 0! ution apparatus such as the des ft eed of agitation, performance prec! of the apparatus, ete. Factors relating to the dissolution fluid such as — composition, viscosity, volume, ined constant temperature: and maintenance of nk (drug concentration in solution maintai ata low level) or nonsink conditions (gradual increase 1n the drug concentration in the dissolution medium). Process parameters: such as method of introduction of dosage form, s changing the dissolution fluid, etc. olution apparatus has evolved gradu ersatile, microprocessor controlled and fully automated inst fied in a number of ways. Based on the absence or presence of sink conditions, th? crincipal types of dissolution apparatus 1. Closed-compartment apparatus under nonsink conditions. The'di e.g., beaker type apparatus. Open-compartment apparatt column which is brought in continuous contact W (perfect sink condition). 3. Dialysis systems ¢ ‘The systems are used fer very poorly aqueous: soluble drugs for which require largevolume. ‘of dissolution = maintenance of sink conditions which would otherwise, fluid.) 1p I > of Beaker Methods— «¢ with a forced convection mixing mechanism. ‘These include all CEN ne tively large volume of the dissolutin ined in a beaker or ing mechanism. Rotating Basket Apparatus (Apparatus De Iti basically a closed compartment, beaker tyPe apparatus comprising of a cylind! vessel with hemispherical bottom of one litre capacity partially immersed in a water bath to maintain the temperature at 37°C. A cyclindrical basket made of 22 mesh to hold the dosage form is located centrally in the vessel at a distance of 2 cm from the bottom and rotated by a variable speed motor through a shaft. The basket should remain in motion during drawing of samples. All metal parts like ating to the d ¢ of the container, nature of ampling techniques, ally and considerably from a simple beaker type ‘rument. The devices can be = are two a limited volume apparatus operating of the container, : Tt is basically the size jissolution fluid is restrained to tained ina tig the one in which the dosage form is co? yn medium th fresh, flowing dissolutio TT Scanned with130 basket and shaft are made of stainless steel 316. (Fig. 5.2). Rotating shalt 25-150 rpm.) <——— 46 [=— Sampling port <— J [—> Onelitertlask <— Dissolution > medium at 37°C < {—> Basket 22 mesh Paddle + Distance of 2em, | Dosage form Rotating Basket apparatus Rotating Paddle apparatus . Schematic represemaion of afficial dissoluiion apparatus forced convection non-sink ype, ting Paddle Apparatus (Apparatus II) ~ ‘The assembly is same as that for apparatus I except that the rotating basket dle which acts as a stirrer. The dosage form is allowed to sink to the bottom of the vessel “small, loose, wire helix may be attached to the dosage form that would otherwise float. Dissolution Medium : Solvents specified in the individual Monograph are used. If te dissolution medium is a buffered solution adjust the solution so that its pH is within 0.05 units the pH specified in the monograph. ~ Interpretation : Unless otherwise specified in the individual mon are met if the quantities of active ingredients dissolv. Fig. is replaced wi lograph, the requirement ed from the-units tested cObferth 1S the areepbany ine acceptance table. Continue testing through the three stages unless the resule Contom ateither S, or S,. The quantity, Q is the amaint of dissolved active gtedient specified inthe individual monograph; expressed as a percentage of the labelled content: Both the 5% and 15% values in the acceptance table are Percentages of the labelled content so that these values and Qare in the same terms. a USP Dissolution Acceptance Criteria . Number Stage Tested Acceptance Criteria Ss, 6 Each unit is not less than Q + 5%. S; 6 Average of 12 units (S, +S.) is equal to or gi than Q and no unit is less than Q— 15%. S; 12 Average of 24 units (S, + S, +°S,) is equal tot greater than Q and not more than 2 units are than Q- 15%, 3WODS Jarge number of dissolution 1 ‘ned their popula hods which hav on of the compendia d Flask-Stirer Method Rotating and Static Dise Method Z Fig. 5.3. Non-official Methods of Measuring atBctaion rate. pakstirrer Method “ wis around botromed fas is Wes pinerverps © avoid tHe problems that- may: aos of the flat bottom of a breaker. gotatiag Filter/Stationary Basket Method fone of the main disadvantages of the rotating basket method is the possi i screen, the filter ‘assembly, oc bath- Op the other hand {a°pFOTEM, the possibity of fl ating, tablets/particles. Pr the bottom of the flask ‘constitute distinct magnetically embly and ‘cloth basket in which the dosage Fan is placed: Fndrawn through the spinnin ine system provides ‘and non-turbulent agitation that is cessenti iducible results. Italso "ofthe bulk fluid with miifmum abrasion to {he solid dosage form. Freercen used for the DASKet Hoe constantly spinning NET TS possibility em. It has been criticized, however Because of its complexit ‘dcleaning. * deficiencies. 1 ity and the ustained Release Formulations oa wus used for the determination of the dissolution s. sis of 12. small bottles 2 ‘The whole assem constant temperature WAC = GO mi of dissolution Turd which is decane tough 40 mesh sereen © and is replaced by Wesh fluid. Usually five uids of different pH are quilized : pF for H 1125 for | hour, PHA.S 10° 1 shouts, pH Tet s hours and finally pH7-5 for 2 hours for a total idigsotution time of 7:0 TOUS:“S 2 VBE Fg ry, 4, Rotating and Statie Dise Methods’ In these methods the drug that is to he assessed for rate of dissolution is compresse non-disintegeating dise. This is mounted in a holder so that only one Face of the disc is exper, holder and disc are immersed in the dissolution medium and either held in a fixed posiiee static disc method or rotated at a given speed in the rotating disc method. Samples of dj. medium are removed after known times, filtered and assayed. Inboth methods, itis assumed that the surface area, from which dissolution can on area can be determined, This is referred to as the intrinsic dissolution rate (as explained in, 1. preformulation). In other methods the surface area of the drug that is available for disse changes considerably during the course of the determination because the dosage disintegrates into many smaller particles and the size of these particles then decreases as, Proceeds, Since these changes are not usually monitored, the dissolution rate is measured of the total amount of drug dissolved per unit time. It should be considered that different dissolution rate methods yield different results but 21, changes in the experimental variables in a given method are likely to lead to changes in the re This is important since dissolution rate tests are usually performed in a comparati determine, for example, the difference between two polymorphic forms of the same compo between the rate of release of a drug from two formulations. Thus, standardization of the experimen methodology is essential if such comparisons are to be meaningful. 5. Open Flow-Through Dissolution Systems In open flow through methods (also known as open compartment methods), the dosage fom: is contained in a small vertical glass column with built in filter throug which a continuous flow the dissolution medium is circulated upward at a specific rate from an outside reservoir “peristaltic or centrifugal pump. The dissolution fluid is usually collected in a separate reservorss leaves the dissolution cell and thereby the dosage form is continuously exposed to fresh solvex (non-cumulative mode) and a perfect sink condition is maintained. If a sink condition could esis be met using a limited volume of dissolution medium, the circulating fluid can be routed back tote original reservoir (cumulative mode). ‘The open flow methods have several advantages over the other methods. Because the apparatus utilizes no stirring mechanism, the dosage form and drug particles are continuously exposed to2 homogeneous nonturbulent laminar flow that can be precisely controlled. All the problems @ ~wobbiing, shaft eccentricity, verticity, vibration, stirrer position etc., simply do not exist. Also, the turbulent solvent flow associated with stirring mechanisms imparts variable degrees of physical abrasion of the solids but is avoided here. ‘The open flow-through septem, however, has its own disadvantages, the most important of which is the tendency of the filter to clog because of the unidirectional flow. Pressure tends to build near the end of the run and in many cases, it is necessary to have built-in pressure tranoducess and a feedback mechanism to increase the pressure gradually in order to keep the flow rate constant Different types of pumps, such as the peristaltic and centifugal varieties, have been shown to givé different dissolution results weiCE EVALUATION METHODS Had a variation of the flow-through concept, is a closed cot 7 cpation of a miniaturized rotating basket with a el Coltumn type system. The system is a : : ‘ losed flow-throu ‘uration of the drug at an acceptable range for quantitative deemien ee pientte omation in Dissolution Testing « : pye to the large amount of testing required in dete gation of the process seemed almost a necessity and emecause of the modular nature of the dissolutior of tl t n apparatus, automation can be easily shed in different ways and by various techniques, up of the apparatus, media preparation and introduction of the dosage forms mostly are sage manually. The rest of the process including the withdrav of the sample, maintenance of a ein pH or of sink conditions, assay performance and data acquisition and calculations ae in | fe cases fully automated, The automation process not oly saves money, time and effort on he \ ‘of the analyst but more significantly it improves the ‘overall reliability and enhances: Yi mining the dissolution rate of drugs, not simply a convenience to the analyst. eat : i i semi 5" © yeibility of the testing procedures, Several commercial companies have als introduce pro y ally automated dissolution systems meTITVAT ENCE (2~ Scanned with