Choice of rotation speed (rpm) for bio-relevant drug dissolution testing using a crescent-shaped spindle.

Recently a new crescent-shaped spindle has been proposed to address the issues related to poor hydrodynamics of the USP paddle apparatus and its associated artifacts of high variability and lack of bio-relevant results. For improved comparison of drug dissolution characterization, it is highly desirable to conduct testing using common experimental conditions such as spindle rotation speed. A study was conducted in which different products were tested using the crescent-shaped spindle to propose a common rpm speed for improved comparative drug dissolution testing. Conventional- (200 mg) and extended-release (200 and 400 mg) carbamazepine tablets of multiple brands and amoxicillin capsules (250 and 500 mg) were analysed using the crescent- shaped spindle at 25, 50 and/or 75 rpm. Drug release was evaluated for 1.5h for amoxicillin and for 3.0 and 24h for conventional- and extended-release carbamazepine tablets products respectively. The dissolution media used were 0.05 M phosphate buffer for amoxicillin capsules and water containing 0.5% sodium lauryl sulphate for carbamazepine tablet products. All products showed characteristic drug release profiles, reflecting the fast and slow drug release natures of the products tested with complete drug release within expected time durations. Based on an expected maximum drug release criterion of 85% in a reasonable time, at a relatively slow drug release rate and within a dosing interval, a spindle speed of 25 rpm was found to be the most appropriate. Thus, it is concluded that drug products can be analysed using a single spindle type (crescent) with a single rpm (25) which would, not only result in simpler dissolution procedures, but also provide enhanced efficiencies from economical and regulatory aspects.     

Improved drug dissolution and product characterization using a crescent-shaped spindle

Drug release characteristics of two amoxicillin capsule products, 250 and 500 mg strength each, have been described using USP Paddle and crescent-shaped spindles. Using the same spindles, dissolution experiments were conducted with USP disintegrating (prednisone) and non-disintegrating (salicylic acid) calibrator tablets. Dissolution tests were conducted at 50 and 25 rev min(-1) using USP Paddle and crescent-shaped spindles, respectively. In all cases, even with the higher 50 rev min(-1), lower percent drug release results were observed with the Paddle spindle than with the crescent-shaped spindle, which was operated at 25 rev min(-1). The observed lower dissolution for amoxicillin capsule products (< 36 vs > 87% at 30 min) and USP prednisone calibrator tablets (45.5 vs 99.8% at 30 min) with Paddle spindles appeared to occur because of the accumulation of the disintegrated material (cone formation) at the bottom, thus restricting product-medium interaction. Crescent-shaped spindles did not allow any accumulation of the product and provided improved interaction by mixing and stirring, and thus appeared to provide true drug dissolution characteristics of the products. On the other hand, in the case of non-disintegrating USP salicylic acid tablets (18.5 vs 24.4% at 30 min), lower results with Paddle spindles appeared to be because of stagnation of the tablets, which provided poor product-medium interaction for the surface touching the vessel surface. In this case, the crescent-shaped spindles moved the tablets at the base of the vessel, providing improved and efficient product-medium interaction, thus appearing to reflect truer dissolution characteristics of the tablets. The results highlight the possible artifacts of the USP Paddle spindle, which could lead to inaccurate characterization of drug release properties of test products. As reported previously, the artifacts of high variability in results and lack of relevance to product properties appeared to be related to poor mixing and variable hydrodynamics within a dissolution vessel. Results from this study provide further evidence that these artifacts might be addressed adequately using the crescent-shaped spindle, thus resulting in improved drug release as well as better product characterization.     

Comparison of WHO and US FDA biowaiver dissolution test conditions using bioequivalent doxycycline hyclate drug products

Objectives The dissolution characteristics of immediate‐release doxycycline hyclate products with certified in‐vivo bioequivalence to the innovator product were tested with a view to possible application of biowaiver‐based approval. Methods Five products were tested using US Pharmacopeia Apparatus 2: Antodox 100 mg hard gelatin capsules, Doxycyclin AL 100 T tablets, Doxycyclin‐ratiopharm 100 soft gelatin capsules, Doxycyclin STADA 100 mg tablets and Doxy‐Wolff 100 mg tablets. Three compendial buffers were used as dissolution media: simulated gastric fluid without pepsin, pH 1.2, acetate buffer, pH 4.5, and simulated intestinal fluid without pancreatin, pH 6.8. Results were obtained at two paddle speeds recommended for biowaiver applications: 75 rpm (World Health Organization; WHO) and 50 rpm (US Food and Drug Administration; US FDA). Key findings The results for the tablets and hard gelatin capsules indicate that a paddle speed of 75 rpm is more representative than 50 rpm, since 75 rpm generates dissolution profiles corresponding more closely to the in‐vivo profiles than those at 50 rpm. For evaluating soft gelatin capsule formulations with lipid fill, both US FDA and WHO methods were found to be over‐discriminating. Conclusions Bioequivalence of immediate‐release doxycycline hyclate tablets and hard gelatin capsules, but not soft gelatin capsules, can be evaluated in vitro using the biowaiver dissolution test conditions specified by the WHO.     

Cause of high variability in drug dissolution testing and its impact on setting tolerances.

Considering a variable mixing/stirring and flow pattern in a drug dissolution vessel as a likely source of high variability in results, experiments were conducted using USP paddle apparatus by placing (aligned to the walls) a metal strip (1.7 mm thickx6.4 mm wide) in a dissolution vessel. The metal strip forces the undisintegrated tablet to settle about 3 mm away from the centre, facilitates spread of disintegrated material and diminishes the cone formation at the bottom of the vessel. To assess the impact of this altered environment in the vessel, but still maintaining the vessel dimensions within required specifications, drug release characteristics were evaluated for products having different formulation/manufacturing attributes. Tests were conducted with calibrator tablets (USP prednisone and salicylic acid tablets and FDA proposed NCDA No. 2 prednisone tablets) and two commercially available products (250 mg amoxicillin capsules and 5 mg glibenclamide tablets). Except for the glibenclamide tablet product, all products gave significantly (P<0.01) higher dissolution results with vessels containing metal strip than without. The extent of increased dissolution with the metal strip varied from product to product i.e. USP prednisone tablet was the smallest (14.4%) and NCDA No. 2 was the largest (88.4%). Based on the results obtained from this study, it is concluded that employing the current apparatuses, in many cases products will provide lower than anticipated results which may not be reflective of the product drug release characteristics. Test-to-test variability, within or between laboratories, can also be very high depending on the settling position of the product once dropped in the vessel and/or due to slight aberration in the walls of the vessel by altering the extent of spread of disintegrated material at the bottom of the vessel. Thus, dissolution testing will require wider tolerances to be useful for comparison of batch-to-batch or interlaboratory results.     

A better dissolution method for ranitidine tablets USP

Ranitidine tablets USP showed variable intra- and inter-lab dissolution results. In order to ascertain the reason for this behavior, ranitidine tablets USP produced by (BIPI) Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, and Zantac Tablets (brand of ranitidine USP), Glaxo Inc., Research Triangle, NC, were subjected to the compendia (USP) dissolution testing using paddle and basket apparatus. Two potencies of tablets 150 mg and 300 mg were tested. Comparison of BIPI tablets and matching Zantac tablets indicated that both brands of ranitidine tablets USP had similar dissolution behavior. When the basket apparatus was substituted for the paddle apparatus the overall rate and extent of tablet dissolution increased, while the individual tablet variability decreased. BIPI 150 mg tablets using the basket apparatus, but at reduced rotational speed of 30 rpm, showed increase in rate and extent of drug dissolved, with less individual tablet variability compared to the paddle apparatus at 50 rpm. The 300 mg tablet (30 rpm/basket apparatus) had an initial slower rate, but then rapidly equaled the paddle apparatus dissolution results, and had less individual tablet variability. Paddle apparatus tablet sinkers were used to prevent tablets from sticking to the bottom of the dissolution vessel. Overall dissolution for all tablets with sinkers showed a trend which was more rapid and complete than tablets without sinkers. Results showed that dissolution artifacts for ranitidine tablets could be reduced by the use of baskets or tablet sinkers.     

Influence of higher rates of agitation on release patterns of immediate-release drug products.

The dissolution procedure serves as a quality control test to assure batch-to-batch uniformity and bioequivalence of a product once the bioavailability of the product has been established. It can also be used to detect manufacturing and/or process variations that could reduce product bioavailability. Dissolution testing must be conducted at an appropriate agitation rate. Tests conducted at high agitation rates may lose the ability to differentiate between good and bad products. Although the effect of high agitation rates has been known for some time, several immediate-release drug products still have United States Pharmacopeia (USP) monograph dissolution procedures that require very high agitation rates. A systematic survey was conducted on marketed tablets of chloroquine phosphate, griseofulvin, hydroxychloroquine sulfate, isocarboxazide, primaquine phosphate, and sulfadiazine. Each of these products has a USP monograph requiring a dissolution test at a paddle speed of 100 rpm. To study the influence of agitation rate on the dissolution rate of these products, dissolution studies were conducted at paddle speeds of 50, 75, and 100 rpm with the USP apparatus 2 (paddle method). The dissolution rate increased with an increase in the agitation rate from 50 to 75 rpm. However, no significant increase in the dissolution rate was noted with an increase in the agitation rate from 75 to 100 rpm. The data support the position that the higher agitation rate of 100 rpm is not necessary for a quality control procedure or a compendial standard for the products tested.     

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine

Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered “highly soluble” across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of carbamazepine as a highly permeable drug. Since the therapeutic and toxic plasma level ranges overlap, carbamazepine is considered to have a narrow therapeutic index. For these reasons, a BCS based biowaiver for IR tablets of carbamazepine cannot be recommended. Interestingly, in nine out of ten studies, USP dissolution conditions (900 mL water with 1% SLS, paddle, 75 rpm) appropriately discriminated among bioinequivalent products and this may be a way forward to predicting whether a given formulation will be bioequivalent to the comparator product.     

Optimization and statistical evaluation of dissolution tests for indinavir sulfate capsules

An optimization, statistically based on t-student test, to set up dissolution test conditions for indinavir sulfate capsules is presented. Three dissolution media, including that reported in United States Pharmacopeial Forum, and two apparatus, paddle and basket, were applied. Two different indinavir sulfate capsules, products A and B, were evaluated. For a reliable statistical analysis eighteen capsules were assayed in each condition based on the combination of dissolution medium and apparatus. All tested media were statistically equivalent (P > 0.05) for both drug products when paddle apparatus was employed at the stirring speed of 50 rpm. The use of basket apparatus at the stirring speed of 50 rpm caused significant decrease in the drug release percent for the product B (P < 0.05). The best dissolution conditions tested, for products A and B, were applied to evaluate capsules dissolution profiles. Twelve dosage units were assayed and dissolution efficiency concept was used, for each condition, to obtain results with statistical significance (P > 0.05). Optimal conditions to carry out the dissolution test were 900 ml of 0.1 M hydrochloric acid as dissolution medium, basket at 100 rpm stirring speed and 260 nm ultraviolet detection.     

Development and validation of new discriminative dissolution method for carvedilol tablets

The objective of the present study was to develop and validate a discriminative dissolution method for evaluation of carvedilol tablets. Different conditions such as type of dissolution medium, volume of dissolution medium and rotation speed of paddle were evaluated. The best in vitro dissolution profile was obtained using Apparatus II (paddle), 50 rpm, 900 ml of pH 6.8 phosphate buffer as dissolution medium. The drug release was evaluated by high-performance liquid chromatographic method. The dissolution method was validated according to current ICH and FDA guidelines using parameters such as the specificity, accuracy, precision and stability were evaluated and obtained results were within the acceptable range. The comparison of the obtained dissolution profiles of three different products were investigated using ANOVA-based, model-dependent and model-independent methods, results showed that there is significant difference between the products. The dissolution test developed and validated was adequate for its higher discriminative capacity in differentiating the release characteristics of the products tested and could be applied for development and quality control of carvedilol tablets.     

Preliminary observations on dissolution and bioavailability of triamterene–hydrochlorothiazide combination products

The dissolution profiles of two brands of triamterene–hydrocholorthiazide (TRM–HCT) combination tablets and two brands of TRM–HCT combination capsules were studied using the USP paddle method at 100 rev min^?1 in acid medium (0·1 N). The tablets represent two products marketed in Germany, whereas the capsules represent the approved innovator's product and an unapproved generic product. The tablets dissolved almost 100 per cent in 15 min whereas the capsules dissolved less than 25 per cent in 60 min. A pilot bioavailability study was carried out in four normal healthy male volunteers. Urine samples were collected over a 48 h period and analysed for TRM, its major metabolite TRM-sulfate, and HCT using HPLC methods. The dissolution characteristics of TRM can be associated with the total drug excretion (absorption) of the product. On the other hand, the excretion (absorption) of HCT was independent of dissolution characteristics of the products. However, in TRM–HCT combination product, there appears to be a 50 per cent reduction in HCT excretion (absorption) when compared to the reported excretion (absorption) from a marketed single-entity product.     

Phenytoin I: in vitro-in vivo correlation for 100-mg phenytoin sodium capsules

Dissolution profiles for 11 brands of phenytoin sodium capsules were carried out by the basket and paddle methods (USP) and the spin-filter method. The results from the dissolution studies have been correlated with observed differences in in vivo parameters (Cmax and tmax). The dissolution by the basket method at 50 rpm in water gave a correlation greater than 0.9. The results suggest the existence of two types of phenytoin sodium products on the market.     

Designing biorelevant dissolution tests for lipid formulations: Case example – Lipid suspension of RZ-50

Biorelevant dissolution test methods for lipid formulations of RZ-50, an experimental Roche compound, were developed and compared with standard compendial methods in terms of their in vivo predictability. Release of RZ-50, a poorly soluble weakly acidic drug, from lipid suspensions filled in soft gelatin capsules was studied in compendial and biorelevant media using the USP Apparatus 2 (paddle method) and the USP Apparatus 3 (Bio-Dis method). Pharmacokinetic data were obtained in dogs after oral administration of a single 2.5mg dose of RZ-50 soft gelatin capsules in the postprandial state. Level A IVIVC analysis and curve comparison of fraction drug dissolved vs. absorbed using the Weibull distribution were used to evaluate the in vitro methods in terms of their ability to fit the in vivo plasma profiles. Very low drug release was observed with the paddle method owing to poor dispersibility of the lipids in the dissolution media, whereas the Bio-Dis method hydrodynamics facilitated release of the drug by emulsifying the formulation in the medium. The best IVIVC was obtained using a dissolution medium representing fed gastric conditions in combination with the Bio-Dis method. Curve comparisons of the fraction drug absorbed and the fraction drug dissolved profiles based on Weibull distribution fits yielded similar results. The Bio-Dis/biorelevant in vitro method appears to be suitable for this type of lipid formulation.     

Dissolution Profile of Mefenamic Acid Solid Dosage Forms in Two Compendial and Biorelevant (FaSSIF) Media

Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial methods available for dissolution tests of mefenamic acid solid dosage forms, i.e. methods of United States Pharmacopeia 37 (USP) and Pharmacopoeia of the People’s Republic of China 2010 (PPRC). Indonesian Pharmacopeia V ed. (FI) adopted the USP method. On the other hand, many researches focused on the use of a ‘biorelevant’ medium to develop the dissolution test method. The aim of this research was to study the dissolution profile of mefenamic acid from its solid dosage forms (caplet and capsule) available in the Indonesian market with three different dissolution medium: USP, PPRC, and biorelevant fasted simulated small intestinal fluid (FaSSIF) media. The tested products consisted of the innovator’s product (available only in caplet dosage form, FN caplet) and generic products (available as caplet and capsule). The dissolution test of the drug products in all dissolution media was performed in 900 mL of medium using apparatus II (paddle) at a temperature of 37°C and rotation speed of 75 rpm, except for the capsule product and for USP medium, both of which tests were done using apparatus I (basket) with rotation speed of 100 rpm. The solubility test of mefenamic acid was carried out in all media at temperature of 37°C. The result obtained from the solubility test showed that the the highest solubility of mefenamic acid was obtained in USP medium (approximately 2 mg/mL), followed by PPRC medium (about 0.5 mg/mL), and FaSSIF medium (approximately 0.06 mg/ml). In the dissolution test, percentage of drug dissolved in in the USP and PPRC media after 45 min for all products reached more than 75%, except for the PN caplet in USP medium which reached only about 44%. Meanwhile, in the biorelevant medium, the percentage of drug dissolved for all products did not exceed 16%. In all dissolution media, the capsule dosage form achieved the highest dissolution rate.     

水飞蓟素原料药及其制剂体外溶出的研究

目的考察水飞蓟素及其制剂(片剂和胶囊剂)的体外溶出度。方法参照美国药典桨法,以人工胃液(SGF)、模拟空腹状态下的肠流质(FaSSIF)、模拟进食状态下的肠流质(FeSSIF)为试验介质分别进行体外溶出实验,采用LC-ESI-MS技术测定水飞蓟素中3种主要成分(水飞蓟宁、水飞蓟宾A和水飞蓟宾B)的体外溶出度。结果水飞蓟素溶解度低,溶出慢,不同制剂在不同介质中的体外溶出速率存在差异,制剂的体外溶出与原料药物的溶出及溶解度有一定的相似性。结论制剂的溶出可以指导体内试验与临床用药,原料药物的溶出及溶解度测定可以指导制剂的溶出测定。     

Dissolution testing of acetylsalicylic acid by a channel flow method—correlation to USP basket and intrinsic dissolution methods

A new modification of the channel flow dissolution method is introduced together with the theoretical basis to extract the solubility and mass transfer parameters from the dissolution experiments. Correlation of drug dissolution profiles in the channel flow apparatus was evaluated with respect to USP basket and intrinsic dissolution methods at pH 1.2 or 6.8. Acetylsalicylic acid (ASA) was studied as a pure drug substance and as three simple tablet compositions with microcrystalline cellulose (MCC) and/or lactose as excipients. The channel flow measurements of 100% ASA tablets correlated well with the results of intrinsic dissolution tests. In the channel flow method as well as in the USP basket method the release of ASA was fastest from the tablet compositions containing lactose, while the slowest dissolution rate was observed with the composition containing MCC as the only excipient. As presumed, the dissolution rate of the weak acid was decreased as the pH of the medium was lowered, which was clearly confirmed also by the three dissolution methods. MCC forms matrix tablets and in the USP basket method the dissolution profiles followed square root of time kinetics indicating that diffusion was the rate-controlling step of ASA dissolution. Also the channel flow results indicated that the dissolution of ASA was controlled by mass transfer. The swelling behaviour of the tablets is different in the channel flow method as compared to the basket method: only one tablet surface is exposed to the dissolution medium in the channel flow system. The contact between the tablet surface and the dissolution medium is more similar between the channel flow and intrinsic dissolution methods.     

Different geometric shaped hydrogel theophylline tablets: statistical approach for estimating drug release

The objective of this study was to develop a mathematical equation for the calculation of drug release from different shaped matrix tablets. By this way, release rate related to the geometric shape could be predicted with the help of the developed mathematical equation. So, drug release could be estimated before the dissolution. Hydroxypropylmethylcellulose (HPMC) E50 as polymer and theophylline as active substance were used in the matrix tablets prepared for this purpose. Matrix tablets in three different geometrical shapes, namely in triangular, cylindrical and half-spherical forms were prepared by using two different drug-polymer ratio (1:0.5, 1:1) and diluent's in three different percentages (0, 20, 40%). Using rotating paddle and basket methods reported in USP XXIII carried out the release rate studies of these tablets. The Higuchi square-root time model best described the dissolution data. Differential scanning calorimetry (DSC) analysis was performed to identify any solid-state inactivation of the drug. The practical benefit of this work is to improve mathematical equation that can be used to predict accurately the required composition and in order to achieve the desired release profiles of different geometric shaped tablets. By using this equation new pharmaceutical products can be easily improved.     

The Use of Experimental Design Principles in Dissolution Method Development: Development of a Discriminating Dissolution Method for Sprycel Film-Coated Tablets

Sprycel® (dasatinib) film-coated tablet is a new medicinal product that was recently launched for the treatment of chronic myelogenous leukemia. Due to the early success of dasatinib in phase I clinical trials, development activities were accelerated significantly to enable wide distribution of this drug to patients. As a BCS class II compound, dissolution was considered a critical quality attribute of dasatinib film-coated tablets and a discriminating dissolution method was required to support tablets intended for Phase II clinical trials and commercial use. A systematic experimental approach was established to rapidly screen media pH, solubility enhancers, and concentration in order to overcome the challenges of a tight timeline and limited study materials. The final validated method utilizes 1,000 mL of pH 4.0 acetate buffer with 1% Triton X-100 with a USP Apparatus II (paddle) rotating at 60 rpm and a HPLC sample analysis.     

Different geometric shaped hydrogel theophylline tablets: statistical approach for estimating drug release

The objective of this study was to develop a mathematical equation for the calculation of drug release from different shaped matrix tablets. By this way, release rate related to the geometric shape could be predicted with the help of the developed mathematical equation. So, drug release could be estimated before the dissolution. Hydroxypropylmethylcellulose (HPMC) E₅₀ as polymer and theophylline as active substance were used in the matrix tablets prepared for this purpose. Matrix tablets in three different geometrical shapes, namely in triangular, cylindrical and half-spherical forms were prepared by using two different drug-polymer ratio (1:0.5, 1:1) and diluent's in three different percentages (0, 20, 40%). Using rotating paddle and basket methods reported in USP XXIII carried out the release rate studies of these tablets. The Higuchi square-root time model best described the dissolution data. Differential scanning calorimetry (DSC) analysis was performed to identify any solid-state inactivation of the drug. The practical benefit of this work is to improve mathematical equation that can be used to predict accurately the required composition and in order to achieve the desired release profiles of different geometric shaped tablets. By using this equation new pharmaceutical products can be easily improved.     

Development and optimization of the drug release determination of iron from iron prolonged release tablets

The aim of this research was to develop and optimize the drug release determination of iron from iron prolonged release tablets. First, solubility characteristics of ferrous sulfate in different aqueous media with a pH in the range of 1 to 8 were studied. According to the results obtained different physicochemical conditions that influence drug release of iron from iron prolonged release tablets were checked. Various aqueous media with a pH in the range of 1 to 7.4, different volumes of dissolution media, various rotation speeds of stirring elements, different dissolution apparatus (apparatus 1/basket apparatus and apparatus 2/paddle apparatus according to USP/Ph. Eur.) were verified. For evaluation of dissolved iron two different methods were checked: atomic absorption spectrometry and redox titration. Redox titration was proved to be a reproducible, discriminatory, selective and cost effective method for evaluation of dissolved iron from iron prolonged release tablets and can be applied in the quality control of solid dosage forms containing iron compounds.     

Evaluation of USP apparatus 3 for dissolution testing of immediate-release products

We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms. Highly soluble drugs, metoprolol and ranitidine, and poorly soluble drugs, acyclovir and furosemide, were chosen as model drugs. The dissolution profiles of both innovator and generic IR products were determined using USP apparatus 2 at 50 rpm and apparatus 3 at 5, 15, and 25 dips per minute (dpm). The dissolution profiles from USP apparatus 3 were compared to those from USP apparatus 2 using the f ₂ similarity test. The dissolution profile from USP apparatus 3 generally depends on the agitation rate, with a faster agitation rate producing a faster dissolution rate. It was found that USP apparatus 3 at the extreme low end of the possible agitation range, such as 5 dpm, gave hydrodynamic conditions equivalent to USP apparatus 2 at 50 rpm. With appropriate agitation rate, USP apparatus 3 can produce similar dissolution profiles to USP apparatus 2 or distinguish dissolution characteristics for the IR products of metoprolol, ranitidine, and acyclovir. Incomplete dissolution was observed for the furosemide tablets using USP apparatus 3. Although it is primarily designed for the release testing of extended-release products, USP apparatus 3 may be used for the dissolution testing of IR products of highly soluble drugs, such as metoprolol and ranitidine, and some IR products of poorly soluble drugs, such as acyclovir. USP apparatus 3 offers the advantages of avoiding cone formation and mimicking the changes in physiochemical conditions and mechanical forces experienced by products in the gastrointestinal tract.