Analysis of Factors Related to Variation in Dissolution Profiles Estimated from Continuously Conducted Dissolution Tests of Generic Products.

The development of generic pharmaceuticals involves a bioequivalence study to ensure the therapeutic equivalence of the test formulation to the original innovative product. The formulation characteristics of generic products are expected to be maintained in the long term after approval. This study analyzed the factors contributing to the changes in the dissolution profiles of approved products during their life cycles. Cumulative data on the dissolution similarity of 1675 products of 127 ingredients tested by official laboratories in Japan were assessed according to Japanese bioequivalence guidelines with slight modifications. The products showing dissimilarities in dissolution profiles were analyzed for reporting year, therapeutic category, co-development, physical properties of the active pharmaceutical ingredient (API), and suspected reasons for dissolution change. The increase in the number of dissimilar products is related to the co-development of generic products. Although the solubility of the API was not associated with the dissolution change in the analysis of the total dissolution data, control of the API particle size is suggested to be important for drugs with poorly soluble APIs. Additionally, a risk factor for dissolution changes in the test solutions at a certain pH was the presence of acidic or basic residues. These results indicate the importance of proper development through a thorough evaluation of the formulation and process factors affecting the dissolution properties throughout the product lifecycle.

A reversed-phase-high performance liquid chromatography method for simultaneous determination of paracetamol, caffeine, drotaverine HCl and their related impurities with dissolution profiling of their tablets and greenness profile assessment.

A sensitive, specific and eco-friendly reversed-phase-HPLC method was developed and validated for the determination of paracetamol, caffeine and drotaverine HCl along with their related impurities. The separation was accomplished using an X-bridge C18 column (5 µm; 250 mm × 4.6 mm inner diameter) and a green mobile phase consisting of methanol and 0.02 M phosphate buffer at pH 5.0 in the gradient elution mode. The detector used was a diode array detector. The proposed method was validated in accordance with the International Conference on Harmonisation guidelines. Linear regressions were found in the range of 1-100, 1-100, 2-60, 1-20, 0.50-30 and 1-15 µg/mL for paracetamol, caffeine, drotaverine HCl, p-aminophenol, theophylline and 3,4-dimethoxyphenylacetic acid, respectively. The suggested method was successfully applied for the determination of the studied drugs in their tablet dosage form without interference from any excipients. No discernible difference was found between the obtained results and official or reported methods, statistically, in terms of both accuracy and precision. Dissolution profiling of the studied tablet was also performed using the suggested procedure. Moreover, the greenness profile was assessed using three different tools, namely, the National Environmental Methods Index, the Analytical Eco-Scale and the Analytical GREEnness Metric Approach. The acquired results assert the agreement of the assay with green chemistry principles.

In Vitro-In Vivo Correlation of Tianeptine Sodium Sustained-Release Dual-Layer Tablets.

Tianeptine tablets are currently marketed to be designed for immediate-release tablets. The tianeptine has a short half-life, making it difficult to design for sustained-release tablets and achieve bioequivalence with the tianeptine immediate-release tablet (Stablon®). We established the in vitro-in vivo correlation (IVIVC) of three formulations of tianeptine sustained-release tablets according to their granule size. To evaluate sustained drug release, in vitro tests were performed in pH 1.2 media for 24 h. In vivo pharmacokinetic analysis was performed following oral administration of reference drug and test drug to beagle dogs. The dissolution profile revealed delayed release as the size of the granules increased. The dissolution results were confirmed in pharmacokinetic analysis, showing that the half-life was delayed as granule size increased. The final formulation and reference drug showed an equivalent area under the curve (AUC). Through this, IVIVC was established according to the size of the tianeptine sodium granules, which is the purpose of this study, and was used to predict in vivo pharmacokinetics from the formulation composition. This approach may be useful for determining optimal formulation compositions to achieve the desired pharmacokinetics when developing new formulations.

Influencing factors on gelatin matrix for chlorhexidine delivery.

OBJECTIVE: The objective was to evaluate the influencing factors in the fabrication of gelatin matrix (gelatin chips) for drug delivery. The attributes affecting drug release characteristics of the gelatin products were examined. SIGNIFICANCE: Understanding the attributes that affect drug release from gelatin matrix could provide the knowledge base for the development, manufacturing, and performance evaluation of gelatin-based drug products for sustained drug delivery. METHODS: Chlorhexidine (CHX) was the model drug in the gelatin-product testing. The gelatin products were fabricated by two methods: a single-pot mixing of all the components and a two-step gelatin crosslinking followed by drug loading. Different gelatin types (Type A porcine and Type B bovine), glutaraldehyde (GTA) crosslinking conditions, glycerin concentration, and CHX concentration in drug loading and loading time were used to fabricate the products. The cumulative amounts of CHX release from the gelatin products were determined using in vitro release testing (IVRT). RESULTS: The attributes affecting CHX release from the gelatin products were gelatin type, GTA crosslinking, and CHX loading concentration. The fabrication methods (two-step method of gelatin crosslinking and drug loading by equilibration vs. direct mixing of the components) also affected CHX release. Other attributes such as glycerin and CHX loading time did not show significant effects on drug release under the conditions studied. In addition, the results in the two IVRT methods employed in this study were comparable. CONCLUSION: Gelatin products of qualitative (Q1) and quantitative (Q2) differences could lead to different drug release behaviors. Drug release was also affected by the ingredient mixing steps during gelatin chip fabrication.

Errors in reporting on dissolution research: methodological and statistical implications.

OBJECTIVE: In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. METHODS: The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. RESULTS: Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. DISCUSSION AND CONCLUSION: A clearer description of the procedures would undoubtedly increase the quality of papers in this area.

Long-Term Physical Stability of Amorphous Solid Dispersions: Comparison of Detection Powers of Common Evaluation Methods for Spray-Dried and Hot-Melt Extruded Formulations.

Although physical stability can be a critical issue during the development of amorphous solid dispersions (ASDs), there are no established protocols to predict/detect their physical stability. In this study, we have prepared fenofibrate ASDs using two representative manufacturing methods, hot-melt extrusion and spray-drying, to investigate their physical stability for one year. Intentionally unstable ASDs were designed to compare the detection power of each evaluation method, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and dissolution study. Each method did not provide the same judgment results on physical stability in some cases because of their different evaluation principles and sensitivity, which has been well-comprehended only for one-component glass. This study revealed that the detection powers of each evaluation method significantly depended on the manufacturing methods. DSC was an effective method to detect a small amount of crystals for both types of ASDs in a quantitative manner. Although the sensitivity of XRPD was always lower compared to that of DSC, interpretation of the data was the easiest. SEM was very effective for observing the crystallization of the small amount of drug for hot-melt extruded products, as the drug crystal vividly appeared on the large grains. The dissolution performance of spray-dried products could change even without any indication of physical change including crystallization. The advantage/disadvantage and complemental roles of each evaluation method are discussed for deeper understanding on the physical stability data of ASDs.

Formulation and Characterization of Electrospun Nanofibers for Melatonin Ocular Delivery.

The poor ocular bioavailability of melatonin (MEL) limits the therapeutic action the molecule could exert in the treatment of ocular diseases. To date, no study has explored the use of nanofiber-based inserts to prolong ocular surface contact time and improve MEL delivery. Here, the electrospinning technique was proposed to prepare poly (vinyl alcohol) (PVA) and poly (lactic acid) (PLA) nanofiber inserts. Both nanofibers were produced with different concentrations of MEL and with or without the addition of Tween® 80. Nanofibers morphology was evaluated by scanning electron microscopy. Thermal and spectroscopic analyses were performed to characterize the state of MEL in the scaffolds. MEL release profiles were observed under simulated physiological conditions (pH 7.4, 37 °C). The swelling behavior was evaluated by a gravimetric method. The results confirmed that submicron-sized nanofibrous structures were obtained with MEL in the amorphous state. Different MEL release rates were achieved depending on the nature of the polymer. Fast (20 min) and complete release was observed for the PVA-based samples, unlike the PLA polymer, which provided slow and controlled MEL release. The addition of Tween® 80 affected the swelling properties of the fibrous structures. Overall, the results suggest that membranes could be an attractive vehicle as a potential alternative to liquid formulations for ocular administration of MEL.

Exploration of Neusilin® US2 as an Acceptable Filler in HPMC Matrix Systems-Comparison of Pharmacopoeial and Dynamic Biorelevant Dissolution Study.

Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10-30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices' evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10-20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms.

Nano-Silica Carriers Coated by Chloramphenicol: Synthesis, Characterization, and Grinding Trial as a Way to Improve the Release Profile.

Silica nanoparticles were applied as the carrier of chloramphenicol (2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide), and were loaded in a 1% carbopol-based gel (poly(acrylic acid)), which allowed obtainment of an upgraded drug form. The samples of silica materials were obtained by means of modified Stöber synthesis, and their morphological properties were analyzed using Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) method, elemental analysis (EA), thermogravimetric analysis (TGA), analysis of the specific surface properties, X-ray diffraction study (XRD), scanning electron microscope (SEM), and dynamic light scattering (DLS) methods, which permitted the selection of the drug carrier. The two obtained silica carriers were coated with chloramphenicol and loaded into 1% carbopol gel. The release studies were then performed. The release results were evaluated using mathematical models as well as model-independent analysis. It was found that the modification of the synthesis of the silica by the sol-gel method to form a product coated with chloramphenicol and further grinding of the silica material influenced the release of the active substance, thus allowing the modification of its pharmaceutical availability. The change in the parameters of silica synthesis influenced the structure and morphological properties of the obtained silica carrier. The grinding process determined the way of adsorption of the active substance on its surface. The studies showed that the proper choice of silica carrier has a considerable effect on the release profile of the prepared hydrogel formulations.

Formulation of Levocetirizine-Loaded Core-Shell Type Nanofibrous Orally Dissolving Webs as a Potential Alternative for Immediate Release Dosage Forms.

Several applications of nanofiber-based systems are based on their corresponding functionality-related properties, which often cannot be satisfied by a fiber web with a monolithic structure because of the various physicochemical properties and amounts of embedded compounds. Therefore, one of the main directions in the development of fiber systems is creating core-shell type complex fiber structures that can provide application-specific properties to the fiber matrix. The present study aimed to formulate levocetirizine-loaded core-shell type hydrophilic polymer-based fibrous systems. The core phase contained the antihistamine levocetirizine, while the permeation enhancer (Na-taurocholate), the local pH regulator (citric acid), and the cyclodextrin used as a taste masking agent were included in the shell phase of the fibrous formulation. Scanning electron microscopy images indicated that a randomly oriented homogeneous fibrous structure was obtained, while the Raman mapping and chemometric analysis confirmed the partially formed core-shell structure. A fast release rate of the antihistamine drug from the complex structural fibrous system was obtained (within 1 min complete dissolution can be observed) due to its increased surface area to volume ratio and its more favorable wettability properties, which consequently allows for more erosion. The masking properties against the unpleasant bitter taste of API of the formulated complex nanostructure were confirmed by the results of the electronic tongue. The formulated complex nanostructure enabled fast and complete release of the API, providing a potential enhancement in the rate and extent of absorption while masking the unpleasant taste of levocetirizine, which has a high impact on the patient adherence. All in all, the results show that the developed orally dissolving fibrous web formulation can be a potential alternative to the commercially available orally disintegrating tablets.

Celecoxib Crystallized from Hydrophilic Polymeric Solutions Showed Modified Crystalline Behavior with an Improved Dissolution Profile.

The crystallization technique has been established as a cost-effective and simple approach to improve the dissolution rate and oral bioavailability of poorly soluble drugs. This study was carried out to study the effect of some selected hydrophilic polymers such as methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, and carboxymethyl cellulose on the crystal behavior and dissolution properties of celecoxib (CLX), a common nonsteroidal anti-inflammatory drug. Structural and spectral characteristics of crystallized CLX have been studied by Fourier transform infrared (FTIR) spectroscopy, diffraction scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. From FTIR and DSC analysis, no significant shifting of peaks or appearance of any new peaks (for polymers) were observed, which indicated the absence of any major interaction between drug and polymers as well as the absence of polymers in the final crystallized product of CLX. The XRD analysis showed a change in crystalline morphology to some extent. The dissolution rate of crystallized CLX in the presence of polymers (particularly with HPMC) was significantly improved compared with plain CLX. The improved dissolution profile of the experimental CLX crystal products could be an indication of improved bioavailability of CLX for better clinical outcome.

Effects of Different Drying Methods on the Characterization, Dissolution Rate and Antioxidant Activity of Ursolic Acid-Loaded Chitosan Nanoparticles.

To improve the water solubility of ursolic acid (UA), UA-loaded chitosan nanoparticles were firstly prepared by the ionotropic gelation method and dried by freeze drying (FD), microwave freeze drying (MFD) and spray drying (SD). The characterization of UA-loaded chitosan nanoparticles was performed with particle size, drug loading (DL), scanning electron microscope (SEM), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), dissolution studies and antioxidant activity. The results demonstrated that UA was successfully encapsulated into chitosan nanoparticles using sodium tripolyphosphate (TPP) as a cross-linker, with a 79% encapsulation efficiency. The spray-dried, UA-loaded chitosan nanoparticles had the lowest drug loading (11.8%) and the highest particle size (496.9 ± 11.20 nm). The particle size of UA-loaded chitosan nanoparticles dried by MFD and FD was lower, at 240.8 ± 12.10 nm and 184.4 ± 10.62 nm, respectively, and their antioxidant activity was higher than those nanoparticles dried by SD. Moreover, the drying time and energy consumption of UA-loaded chitosan nanoparticles dried by MFD and SD were lower than that of FD. The dissolution rates of UA-loaded chitosan nanoparticles prepared by FD and MFD were 60.6% and 57.1%, respectively, in a simulated gastric fluid, which was a greater value than SD (55.9%). Therefore, the UA-loaded chitosan nanoparticles encapsulation method, combined with MFD technology, showed a promising potential to improve the water solubility of UA.

Relevance of Liquid-Liquid Phase Separation of Supersaturated Solution in Oral Absorption of Albendazole from Amorphous Solid Dispersions.

Amorphous solid dispersion (ASD) is one of the most promising formulation technologies for improving the oral absorption of poorly soluble drugs, where the maintenance of supersaturation plays a key role in enhancing the absorption process. However, quantitative prediction of oral absorption from ASDs is still difficult. Supersaturated solutions can cause liquid-liquid phase separation through the spinodal decomposition mechanism, which must be adequately comprehended to understand the oral absorption of drugs quantitatively. In this study, albendazole (ALZ) was formulated into ASDs using three types of polymers, poly(methacrylic acid-co-methyl methacrylate) (Eudragit) L100, Vinylpyrrolidone-vinyl acetate copolymer (PVPVA), and hydroxypropyl methylcellulose acetate succinate (HPMCAS). The oral absorption of ALZ in rats administered as ASD suspensions was not explained by dissolution study but was predicted using liquid-liquid phase separation concentration, which suggested that the absorption of ALZ was solubility-limited. The oral administration study in dogs performed using solid capsules demonstrated the low efficacy of ASDs because the absorption was likely to be limited by dissolution rate, which indicated the importance of designing the final dosage form of the ASDs.

Tailoring immediate release FDM 3D printed tablets using a quality by design (QbD) approach.

The aims of this work were to produce immediate release printed tablets using fused deposition modelling (FDM) technique and to systematically explore the effects of different compositions on drug release by Quality by Design approach. Screening studies of various drug loadings and excipients were conducted by hot melt extrusion and FDM printing to set up the appropriate limit of each independent factor (critical material attribute, CMA) in Design of Experiment. This study demonstrated that the use of polymeric mixture containing different theophylline loadings (10, 30 and 60% w/w) in combination with multiple pharmaceutical polymers (hydroxy propyl cellulose (HPC), Eudragit® EPO, Kollidon® VA 64) and disintegrant (sodium starch glycolate) were successfully hot melt-extruded and FDM printed with no plasticizer. Rheological measurement was performed to understand the critical process parameters (CPP) while the mechanical property of extrudable and printable filaments was investigated by 3-point test for the formulation development. Surprisingly, HPC were found to be superior as a flexibility modifier in all printable filaments. A range of pharmaceutical characterizations were examined to ensure the critical quality attributes (CQA). Characteristic dissolution profiles were obtained. D-optimal mixture design of 17 formulations suggested that theophylline release was considerably affected by the combined action of different excipients and could predict the optimum formulation with the required quality target product profile (QTPP) in pharmacopoeia (85% release at 30 min). Therefore, this can be a useful platform to develop immediate release products for a specific group of patients commercially.

Evaluation of Biodegradable PVA-Based 3D Printed Carriers during Dissolution.

The presence of additive manufacturing, especially 3D printing, has the potential to revolutionize pharmaceutical manufacturing owing to the distinctive capabilities of personalized pharmaceutical manufacturing. This study's aim was to examine the behavior of commonly used polyvinyl alcohol (PVA) under in vitro dissolution conditions. Polylactic acid (PLA) was also used as a comparator. The carriers were designed and fabricated using computer-aided design (CAD). After printing the containers, the behavior of PVA under in vitro simulated biorelevant conditions was monitored by gravimetry and dynamic light scattering (DLS) methods. The results show that in all the dissolution media PVA carriers were dissolved; the particle size was under 300 nm. However, the dissolution rate was different in various dissolution media. In addition to studying the PVA, as drug delivery carriers, the kinetics of drug release were investigated. These dissolution test results accompanied with UV spectrophotometry tracking indirectly determine the possibilities for modifying the output of quality by computer design.

Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals.

Cyclodextrins (CDs) form complex crystals with drugs and improve physicochemical properties of drugs. However, only few reports have summarized relationships between crystal structures of drug/CD and dissolution behavior. In this study, we developed cimetidine (CIM)/CD complex crystals to achieve sustained drug release and investigated the relationship between the dissolution behavior of CIM/CD complexes and their crystal structures. CIM and 3 types of CDs (α-, ß-, and γ-CD) formed a complex crystal when subjected to solvent mixing. The CIM/CD complexes had a highly reduced dissolution rate compared to that of the physical mixture of CIM and CD. ß-CD improved the solubility of CIM, whereas γ-CD decreased its solubility. Based on the phase solubility diagram, CIM and α-, ß-, and γ-CD indicated A-type positive (AP) and AL deviation, and B-type limited solubility (BS) profiles, respectively. In γ-CD, the saturated concentration of CIM decreased owing to the formation of a low-solubility complex with CIM. CIM/α-CD formed cage-type crystals, and CIM/ß-CD and CIM/γ-CD formed channel-type crystals. The dissolution rate constant (k) of CIM/α-CD and CIM/ß-CD were 0.045 and 0.04 h-1, respectively. CIM/γ-CD and CIM/ß-CD displayed channel-type crystals; however, the channel-type crystals of CIM/γ-CD were stabilized by the presence of additional water molecules.

Eutectics and Salt of Dapsone With Hydroxybenzoic Acids: Binary Phase Diagrams, Characterization and Evaluation.

Poor solubility and low dissolution rate of pharmaceuticals in many cases largely limit their bioavailability and efficacy. One of the promising approaches to improve dissolution behavior is to develop new multicomponent solid forms. Herein we use this strategy to synthesize new multicomponent solids of dapsone (DAP), which belongs to BCS class IV, with a series of hydroxybenzoic acid coformers. A new salt of DAP with 2,6-dihydroxybenzoic acid (26DHBA) and 4 eutectics with other hydroxybenzoic acids were reported through comprehensive characterizations using powder X-ray diffraction DSC, and vibrational spectroscopy techniques. The salt formation was evidenced by the presence of ionic interactions detected using FT-IR and Raman spectroscopy, and the stoichiometric ratio was determined to be 1:1. Binary phase diagrams were established to determine the composition of eutectics. The cause for salt and eutectic selection was further understood by computing molecular electrostatic potential (MEP) surface where 26DHBA shows the greatest acidity. Moreover, the powder dissolution study and microenvironment pH measurement reveal that both salt and eutectics of DAP display improvements on the dissolution rate and equilibrium concentration in which the acidity of coformers plays a dominant role. Our findings provide a direction for future coformer screening of multicomponent solids with improved pharmaceutical properties.

Evaluation of impurities and dissolution profiles of illegal antimicrobial drugs encountered in Belgium.

Substandard and falsified (SF) antimicrobials are gaining popularity in both developing and developed countries, posing a growing threat to public health. In general, the evaluation of SF antimicrobial drugs mainly focuses on the identification and quantification of the pharmaceutical active ingredients, ignoring other parameters of drug quality control. This study performed an in-depth characterization and hazard identification of suspected SF antimicrobial medicinal products encountered in Belgium. In this comprehensive evaluation, impurity tests and dissolution studies were carried out. The dissolution profiles of illegal SF antimicrobials were mathematically compared to their genuine counterparts using the f1 and f2 -factor. The results indicated that 17 out of 57 illegal samples contained higher than permitted amounts of impurities and clearly demonstrated low equivalences of dissolution profiles between SF antimicrobials and genuine products. The variations between tablets at the different time points of the dissolution curves were also higher for the SF medicines. Moreover, 11 out of 19 illegal samples failed to meet the dissolution criteria prescribed by the United States Pharmacopeia. As impurities may induce adverse reactions and improper dissolution patterns may be the cause of insufficient drug efficacy, aggravation of illness and even promotion of antimicrobial resistance can be expected.

Dissolution Chamber for Small Drug Delivery System in the Periodontal Pocket.

Existing dissolution chambers have relatively large volume compared to the size of the periodontal pocket. A small volume dissolution method that simulates the physiological release environment for periodontal drug delivery is needed. The objectives were to construct a small, more physiologically relevant, dissolution chamber and investigate the properties of the new dissolution chamber for the assessment of sustained drug release systems in periodontal delivery. Flow-through dissolution chambers were constructed using three-dimensional (3D) printing. Drug release experiments were performed using the dissolution chamber and a commercially available long-acting periodontal insert product, PerioChip®. Similar experiments were performed under more traditional larger volume bulk solution conditions for comparison. Computer simulations and experimental results showed that drug clearance from the dissolution chamber was fast compared to drug release from the periodontal product. Drug clearance from the flow-through dissolution chamber and drug release from the sustained release product in the chamber were related to the dissolution medium flow rate and chamber volume. Drug release in the flow-through chamber was slower than that observed in bulk solution, but approached it when the medium flow rate increased. The presence of trypsin in the dissolution medium enhanced drug release from the product. A flow-through dissolution system was constructed that could evaluate drug release from a sustained release product in a small dimension environment by modifying the flow rate and composition of the dissolution medium.

Structural characterization and dissolution profile of mycophenolic acid cocrystals.

Three novel cocrystals of mycophenolic acid (MPA) with isonicotinamide (MPA-ISO), minoxidil (MPA-MIN) and 2,2'-dipyridylamine (MPA-DPA) as coformers have been prepared successfully by both slow evaporation and liquid-assisted grinding. The structures of these cocrystals show that all the three coformers form hydrogen bonds with the carboxylic acid group of MPA. The cocrystal MPA-ISO possesses remarkably improved solubility and dissolution rate, while two other cocrystals exhibit the opposite characteristics. The solids in the slurry with pH6.8 phosphate buffer and cocrystals remain as the incipient cocrystal after 24h. However, evidence of slight polymerization was shown in the slurry of pH6.8 phosphate buffer with MPA and MPA-ISO cocrystal.