Similar Dissolution Profiles Research Articles

Effect of batch size on the granule properties in planetary centrifugal granulation.

A granulation method using a planetary centrifugal mixer, called planetary centrifugal granulation, has been developed for small-scale production, such as extemporaneous preparation in pharmacies. Although the impact of its operational parameters on granulation is described, the scale effect has not been investigated. Therefore, we aimed to reveal the effects of vessel size and vessel filling rate on granule properties. In this study, ibuprofen 20% granules consisting of lactose, cornstarch, sodium carmellose, and talc were used as model granules. Granulation was performed using geometrically similar containers, 6-58 mL, with a filling rate of 20-70%. After granulation, we monitored the granule properties, for example, median diameter (d50), span of particle size distribution, and sphericity. At filling rates of 40% and 50% in the 58-mL vessel, the granules grew larger in diameter, and at a rate of 30%, the granules showed a higher sphericity. When the filling rate was 30%, d50 became larger and the span decreased as the vessel size increased. The yields of the granules were higher than 95% when using the 12-58 mL vessel. Lastly, the drug content uniformity and drug dissolution behavior of the granules produced in different vessel size were examined. The granules showed similar drug consistencies and drug dissolution profiles. In conclusion, the quality of the products was not affected by changes in vessel size. Thus, pharmacists could prepare and compound the granule formulations with high yield and appropriate quality using an adequate vessel in the same manner.

DISSOLUTION PROFILE SIMILARITY ANALYSES-STATISTICAL PRINCIPLES, METHODS AND CONSIDERATIONS.

The pharmaceutical industry and regulatory agencies rely on dissolution similarity testing to make critical product decisions as part of drug product life cycle management. Accordingly, the application of mathematical approaches to evaluate dissolution profile similarity is described in regulatory guidance with the emphasis given to the similarity factor f2 with little discussion of alternative methods. In an effort to highlight current practices to assess dissolution profile similarity and to strive toward global harmonization, a workshop entitled "In Vitro Dissolution Similarity Assessment in Support of Drug Product Quality: What, How, When" was held on May 21-22, 2019 at the University of Maryland, Baltimore. This manuscript provides in-depth discussion of the mathematical principles of the model-independent statistical methods for dissolution profile similarity analyses presented in the workshop. Deeper understanding of the testing objective and statistical properties of the available statistical methods is essential to identify methods which are appropriate for application in practice. A decision tree is provided to aid in the selection of an appropriate statistical method based on the underlying characteristics of the drug product. Finally, the design of dissolution profile studies is addressed regarding analytical and statistical recommendations to sufficiently power the study. This includes a detailed discussion on evaluation of dissolution profile data for which several batches per reference and/or test product are available.

Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations.

This report summarizes podium presentations and breakout sessions from the second day of the 2019 M-CERSI workshop on In Vitro Dissolution Similarity Assessment in Support of Drug Product Quality: What, How, and When? Presenters from the U.S. Food and Drug Administration (FDA), Health Canada (HC), European Medicines Agency (EMA), Brazilian Health Surveillance Agency (ANVISA), and the pharmaceutical industry shared experiences/concerns with dissolution profile similarity assessment supporting minor/moderate Chemistry, Manufacturing and Control (CMC) changes. Members from regulatory agencies explained that dissolution profile similarity testing is only part of the overall assessment of the acceptability of the proposed changes; decisions are usually made based on aggregate weight of evidence. Scientific shortcomings of f2 were highlighted but no proposal on how to replace it was made. Controlling dissolution timepoint variability and application of pairwise batch-to-batch comparisons (PBC) of dissolution profiles caused considerable debate. Several industry participants suggested increased sample sizes to raise confidence in decision-making and to avoid PBC. They proposed identification of a single mathematical method with predefined acceptance criteria and suggested that dissolution timepoint selection should follow EMA and HC guidance. A majority of meeting attendees favored applying clinically relevant dissolution specifications (CRDS) and dissolution safe space to determine the impact of minor/moderate CMC changes as opposed to dissolution profile similarity assessment via statistical methods. Day 2 of the workshop highlighted the need and opportunities for global harmonization including variability, timepoint selection, role of CRDS, and statistical methods to address the ambiguity globally operating pharmaceutical companies are currently facing.

Switching from batch to continuous granulation: A case study of metoprolol succinate ER tablets

Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. This study investigated the critical aspects of switching from the batch mode of high shear granulation to the continuous operation of twin-screw granulation for extended-release tablets. Metoprolol succinate ER tablets was used as a model ER formulation for this purpose. A central composite design (CCD) was employed to determine the effects of high shear granulator (HSG) parameters, namely impeller speed, granulation time, and binder liquid feeding rate, on the critical granulation characteristics important for product performance. These critical granulation characteristics served as a guide for switching from the batch processing to the continuous operation for achieving the same breaking strength and dissolution for this ER metoprolol tablets.The granulation time was the most critical factor affecting the bulk properties of granules which contributed to tablet dissolution. The higher density and lower compressibility of granules were attained at the longest granulation time of 5.4 min with the fastest liquid feeding rate of 75 g/min. The granules’ density was the primary factor negatively affecting the dissolution of metoprolol tablets. However, the breaking strength of tablets confounded the effect of granules density on metoprolol dissolution. Switching the processing parameters of high shear granulation to twin-screw granulation achieved similar dissolution profiles (F2 greater than 50). The screw speed was not found to affect bulk properties of granules. The root cause of granulation failures in twin-screw granulation, such as premature consolidation, excessive swelling, poor cohesion, inconsistent shearing effects, and formation of deformed agglomerates, were identified. In conclusion, the use of critical granulation characteristics through a performance-based approach of ER tablets facilitated the switching of manufacturing of an ER formulation form batch to continuous operation.

Formulation and Cost-Effectiveness of Fluid Gels as an Age-Appropriate Dosage Form for Older Adults with Dysphagia.

Dysphagia is associated with increased dependency and treatment costs, whereby patients resort to extemporaneous compounding that may further increase the number of adverse events and medical errors. In the management of dysphagia, increasing the bolus viscosity of medication such as fluid gels can be practiced. This study aimed to prepare and characterize the fluid gels as well as to estimate the cost of using fluid gels and compare it to the conventional practice of extemporaneous preparation of thickened liquid. Fluid gels were formulated using gellan gum and determined for physicochemical characteristics and in vitro drug release profile. The cost-based price of the fluid gel was estimated and compared to the cost of administering standard medication as well as administering thickened liquid using thickening powder. Fluid gels exhibited good physicochemical properties with the viscosity within nectar and honey consistency. A similar dissolution profile to the reference was observed for the 0.5% w/v gellan gum fluid gel and exhibiting the Higuchi release model. The price for 100mL unit of 50mg/mL paracetamol/acetaminophen and 20mg/mL ibuprofen fluid gel was estimated to be about USD2.30 and USD2.37, respectively. A dose of 1000mg paracetamol and 400mg ibuprofen fluid gel was estimated to be about USD0.46 and USD0.47, respectively, which is lower than the cost of administering the same dose using extemporaneous thickened liquid. Fluid gels could be a cost-effective formulation for delivering medication in patients with dysphagia and can be developed on a profitable scale.

Artificial intelligence based design of 3D-printed tablets for personalised medicine

A multi-material 3D printing offers nearly endless possibilities for the spatial arrangement of individual materials within the object being printed. In the case of pharmaceutical tablets, the spatial arrangement of individual material domains containing the active pharmaceutical ingredients (APIs) and excipients uniquely defines the release profiles of the APIs. However, the inverse is not necessarily true – identical or very similar dissolution profiles can potentially be obtained from different tablet internal structures, implemented as a combination of domains containing excipients with different individual dissolution rates and different local API concentration. This work presents a computational method based on an Evolutionary Algorithm for the solution of the inverse problem, i.e. finding such tablet internal structure that results in a prescribed dissolution profile of each API contained in the tablet. After testing the algorithm on cases with a known solution, the methodology is applied to a problem of finding tablet structures that result in delayed release and step-wise release profiles, respectively. When combined with patient-specific requirements on drug release profiles, the algorithm can serve as a tool for an automated design of 3D-printed tablets in the framework of personalised medicine.

Dissolution Profile Evaluation of Eight Brands of Metformin Hydrochloride Tablets Available in Jimma, Southwest Ethiopia.

BackgroundDissolution is the critical quality control parameter and used to predict an in vivo oral bioavailability, and it is used to support bio-waiver.AimTo evaluate and compare the dissolution profile of eight brands of metformin HCL 500 mg tablets available in Jimma town, Southwest Ethiopia.MethodsThe study was conducted in Jimma town, Ethiopia. Eight (seven brands and one comparator) metformin HCL 500 mg tablets were included. The dissolution study was conducted as per United States Pharmacopeia, and the dissolution profile was compared by one-way ANOVA, model-dependent and model-independent approaches.ResultsAll of the included tablet brands complied with single-point dissolution study specification. Statistical comparisons of the dissolution profile by one-way ANOVA revealed that all brands had similar dissolution profiles (p=0.89). All of the brands had a similarity factor (f2) >50% and the difference factor (f1) <15. The entire brands followed the Weibull curve approach (the highest coefficient of determination and lowest Akaike Information Criteria) for the release of an active pharmaceutical ingredient.ConclusionAll of the brands complied with single point dissolution study and all of them could be used interchangeably with the innovator drug. All brands followed the Weibull method for the release of the drug substance.

Bioequivalence of Oral Drug Products in the Healthy and Special Populations: Assessment and Prediction Using a Newly Developed In Vitro System "BE Checker".

In order to assess and predict the bioequivalence (BE) of oral drug products, a new in vitro system “BE checker” was developed, which reproduced the environmental changes in the gastrointestinal (GI) tract by changing the pH, composition, and volume of the medium in a single chamber. The dissolution and membrane permeation profiles of drugs from marketed products were observed in the BE checker under various conditions reflecting the inter-patient variations of the GI physiology. As variable factors, initial gastric pH, gastric emptying time, and GI agitation strength were varied in vitro. Dipyridamole, a basic drug, showed rapid and supersaturated dissolution when the paddle speed in the donor chamber was 200 rpm, which corresponds to the high agitation strength in the stomach. In contrast, supersaturated dissolution disappeared, and the permeated amount decreased under the conditions with a slow paddle speed (100 and 50 rpm) and short gastric emptying time (10 min). In those conditions, disintegration of the formulation was delayed, and the subsequent dissolution of dipyridamole was not completed before the fluid pH was changed to neutral. Similar results were obtained when the initial gastric pH was increased to 3.0, 5.0, and 6.5. To investigate that those factors also affect the BE of oral drug products, dissolution and permeation of naftopidil from its ordinary and orally disintegrating (OD) tablets were observed in the BE checker. Both products showed the similar dissolution profiles when the paddle speed and gastric emptying time were set to 100 rpm and 10 or 20 min, respectively. However, at a low paddle speed (50 rpm), the dissolution of naftopidil from ordinary tablets was slower than that from the OD tablets, and the permeation profiles became dissimilar. These results indicated the possibility of the bioinequivalence of some oral formulations in special patients whose GI physiologies are different from those in the healthy subjects. The BE checker can be a highly capable in vitro tool to assess the BE of oral drug products in various populations.

Formulation development and evaluation of duloxetine extended-release tablets

Duloxetine is an anti-depressant drug which is used in depression. The aim of present investigation was to prepare an ER tablet of duloxetine with similar dissolution profile matching to Effexor ER. An immediate release core tablet of 100mg was prepared and it was compression coated using HPMC matrix system. HPMC of three viscosity grades i.e., K4M, K15M, K100M and different concentrations of 15% polymer, 25% polymer, 35% polymer &amp; 45% polymer were taken. With the above polymers by using wet granulation and direct compression process 11 formulations were prepared. The data obtained from in vitro drug release was used to determine the similarity factor between marketed and optimized product. Out of all F11 formulation (K15M 35% polymer) is optimized and is matching with the marketed product.

Assessment of the pharmaceutical equivalence and in vitro dissolution studies of amlodipine tablets marketed in Northern Nigeria

The extensive supply of poor quality and/or counterfeit drug products in many developing countries has made it vital to frequently carry out suitable tests to assess bioequivalence (BE) in a cost-effective manner. This study was intended to assess the pharmaceutical equivalence and dissolution profile of amlodipine 5mg tablets marketed in Jos and Kaduna metropolis. Ten brands of Amlodipine 5mg tablets were obtained from different community pharmacies and evaluated for different quality control parameters such as percent drug content, friability, hardness, thickness, weight uniformity, disintegration time, and dissolution. The results showed that brands F and I failed the test for percent drug content while the rest of the brands passed it. In addition, all the brands passed the disintegrationand friability test while Brands C, F and I did not pass the hardness test. The dissolution profiles of all the brands were similar to the innovator brand at pH 6.8, whereas at pH 1.2, only four brands (B, E, H and I) had similar dissolution profile to the innovator. This study serves to justify for the assessment of in vitro parameters of commercially available amlodipine generics which may aid the prescribers’ decision making.&#x0D; Keywords: Amlodipine; Jos; Tablet properties, Dissolution profile

Exploration of Elephant Foot Yam (Amorphophallus paeoniifolius) Starch: An Alternative Natural Disintegrant for Pharmaceutical Application

Abstract: Aim and Objectives: The aim of the current study is to isolate the starch from elephant foot yam (Amorphophallus paeonifolius) and investigate its potential as a disintegrant in tablet formulation as compare to standard corn starch. The objective of the study is to explore the applications of natural resources and develop an alternative to commercially available starches. Materials and Methods: Starch was isolated by a simple method, evaluated for phytochemical and physico-chemical properties. Tablets were prepared by wet granulation by varying concentrations of elephant foot yam or corn starch in the range of 2.5%, 5%, 7.5% and 10%. Further granules were evaluated for flow properties and tablets were evaluated for post-compression parameters. Results: It was found that the pH of the isolated starch sample was found to be neutral; it exhibited good swelling capacity and fair flow properties. P-XRD pattern showed a C-type diffraction pattern, SEM studies indicated that starch granules had a smooth surface. Granules possessed good flow properties and tablets complied with standard limits of weight variation. Hardness and friability were found in the range of 4.11-4.69 kg/cm2 and 0.11-0.50% respectively. The wetting time was found in the range of 7 to 35 sec for elephant foot yam starch and 16-49 sec for corn starch. Disintegration time for elephant foot yam starch was found to be 28 to 84 sec and for corn starch, it was 40 to 90 sec. Conclusion: Formulations containing elephant foot yam starch showed a similar dissolution profile as that of corn starch. Stability studies were performed on F4 batch and it was found stable for three months. Key words: Elephant foot yam, Corn starch, Disintegrant, Fast Disintegrating tablet, Disintegration time, Wetting time.

Development and Validation of an Eco-friendly HPLC-UV-DAD Method for the Determination of Allopurinol in Pharmaceuticals with Application to In vitro Dissolution Studies

In this study, a sustainable HPLC-UV-DAD method was developed and validated for the determination of allopurinol in tablets and optimization of the dissolution test using factorial design. The separation of the analyte from the sample matrix was achieved in 3.01 minutes in a C8 column (4.6 mm X 150 mm X 5 μm), using mobile phase 0.1 mol L-1 HCl (25%) + ethanol (50%) + ultrapure water (25%) by UV detection at 249 nm. The method presented satisfactory analytical parameters of validation (specificity, selectivity, linearity, stability, precision, accuracy, and robustness), showing no matrix effects. The dissolution test was optimized by complete factorial design 23 and, the optimal conditions were: HCl 0.001 mol L-1, apparatus II (paddle) and 75 rpm. The analytical procedures and dissolution tests were applied to allopurinol tablets marketed in Bahia, Brazil, to evaluate the dissolution studies. The pharmaceuticals had similar dissolution profiles and first-order dissolution kinetics. This new and sustainable HPLC-UV-DAD method is friendly to the environment and can be used for the routine pharmaceutical analysis of allopurinol in fixed dosage forms.

Developing and Featuring Matrix Tablets by Using Gross Linseed Mucilage as a Retardant Polymer

Evaluating the potential of gross Linum usitatissimum L. seed mucilage to be used as a drug release retardant. In order to do so, seeds were subjected to a simple and scalable extractive process comprising few stages, without alcohol-based precipitation. Matrix tablets based on hydrophilic polymers are one of the simplest forms of developing modified release systems. Flaxseeds were added to distilled water at a flaxseed:water ratio of 1:13; the suspension was continuously stirred at room temperature, for 24 h. Flaxseeds were sieved and the gross linseed mucilage was freeze-dried. Subsequently, the sample was analyzed through Fourier transform infrared spectroscopy (IV-TF) at wavelength ranging from 650 to 4000 cm−1. Infrared (IR) spectroscopy analysis has suggested the presence of flaxseed mucilage polymers in the extracted product. Tablets presenting mucilage or HPMC (hydroxypropyl methylcellulose) and tablets without polymer were prepared based on the wet granulation technique. Matrix tablets presenting mucilage or HPMC have shown similar dissolution profiles, as well as similar potential in drug release control. The product extracted from flaxseed under simple conditions, even without undergoing purification process, can have high technological value in the pharmaceutical industry because it has excellent potential to be used as excipient for matrix tablet manufacturing.

Assessment of physicochemical properties and comparison of the dissolution profile of amoxicillin caplets

Background: Marketed drugs must meet the required standards to guarantee product quality. Amoxicillin is a generic compound marketed under various trademarks as copy drugs. Amoxicillin caplets are an immediate release dosage form of BCS class I. An essential aspect of evaluating copy drugs is to assess the equivalence for their treatment to the innovator drugs to ensure the safety and effectiveness of the circulating copy drugs. Objective: The study aims to evaluate the physicochemical properties and compare the dissolution profile of amoxicillin caplets available in the market. Methods: Five amoxicillin caplet products, four test products, and one reference product were tested for their physicochemical properties and dissolution. The dissolution test was carried out with a type II device at a speed of 75 rpm in 900 mL of media buffered at pH 1.2, 4.5, and 6.8 and at a temperature of 37 +/- 0.5degrees celcius. The dissolution profile was analyzed by comparing it with the similarity factor (f2) parameters. Results: Two of the four amoxicillin caplet products had a similar dissolution profile to the reference products, namely products A and B. Products C and D were dissimilar because f2 was lower than 50 at pH 4.5. The caplets tested had almost the same dimensions, and all caplets met the requirements for uniformity of content, hardness, disintegration time, and dissolution. Conclusion: Not all of the amoxicillin caplets in the market have a similar dissolution profile to the reference products. Keywords: caplets, amoxicillin, dissolution, similarity factor

Evaluation of dissolution techniques for orally disintegrating mini-tablets

Mini-tablets are suitable for paediatric as well as geriatric use since they may provide flexible and accurate dosing and administration. Due to the minute tablet size, there is a need for new standardized quality evaluation procedures and conventional techniques may have to be adopted. The main objective of the study was to evaluate different dissolution techniques for orally disintegrating mini-tablets. Dissolution tests using mini-paddle apparatus were compared with standard size paddle apparatus, and the effect of paddle rotation speed was evaluated. Also, the filter choice, and its impact on dissolution, was considered. Sodium salicylate was used as a model drug substance and was mixed with different size fractions of mannitol. The powder mixtures were compacted into 2 mm flat faced tablets. The mini-tablets were characterized regarding weight and content uniformity, tensile strength, friability, disintegration and dissolution. Similar dissolution profiles were obtained with both mini and standard equipment. The paddle rotation speed affected the dissolution profiles; a low paddle speed resulted in a slower dissolution. Furthermore, choosing a chemically inert filter will increase the likelihood of obtaining reliable and accurate results. An appropriately designed dissolution test using mini-paddle apparatus is required prior to further implementation in quality control procedures.

Similarity of dissolution profiles from biorelevant media: Assessment of interday repeatability, interanalyst repeatability, and interlaboratory reproducibility using ibuprofen and ketoconazole tablets

Biorelevant media are increasingly being employed as dissolution media in drug development, including in smaller volumes than 900ml and under non-sink conditions. The objectives were to assess interday repeatability, interanalyst repeatability, and interlaboratory reproducibility of dissolution profiles from biorelevant media, as well as to assess the impacts of biorelevant media production method and biorelevant medium volume on dissolution profiles. Ibuprofen and ketoconazole tablets were subjected to dissolution testing in 500ml, 300ml, and 40ml of fasted state simulated gastric fluid (FaSSGF), fed state simulated gastric fluid (FeSSGF), fasted state simulated intestinal fluid version 2 (FaSSIF-V2), and fed state simulated intestinal fluid version 2 (FeSSIF-V2). f2 was used to assess repeatability and reproducibility of dissolution profiles. Results indicate favorable interday repeatability (83 of 88 comparisons were similar), favorable interanalyst repeatability (19 of 21 comparisons were similar), and favorable interlaboratory reproducibility (10 of 14 comparisons were similar) of dissolution profiles from biorelevant media, with commercial media showing greater interlaboratory reproducibility than ‘from scratch’ media. However, biorelevant medium production had low impact on profiles when one analyst conducted all medium preparations and study procedures at one location. Additionally, biorelevant media detected differences when products were not similar. Overall, biorelevant media showed favorable repeatability and reproducibility performance.

Effect of TPGS surfactant on dissolution sensitivity of a poorly water-soluble drug using high-shear wet granulation

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been widely used in a variety of oral applications to enhance dissolution, solubility, and/or bioavailability of poorly-water soluble drugs. In addition, the use of TPGS could potentially minimize achlorhydric effects typically existing in patients co-administered with proton pump inhibitors (PPI) or H2 receptor blockers. The incorporation of TPGS in tablets, however, can have undesirable effects on compaction, physical stability, and processing. Therefore, the goal of this study was to develop a systematic approach using high-shear wet granulation (HSWG) to effectively incorporate TPGS into solid oral formulations to enhance bioavailability under achlorhydric conditions without tablet defects. TPGS levels were optimized and defined based on dissolution, bioperformance, physical stability, and tablet properties. TPGS-containing HSWG formulations had significantly improved processing and flow properties and outperformed dry granulation formulations in dissolution and bioperformance under achlorhydric conditions. Furthermore, the formulation robustness of the HSWG formulations was demonstrated through similar dissolution profiles despite containing different attributes of a poorly water-soluble drug. Therefore, HSWG formulations with the addition of TPGS can be used to minimize not only achlorhydric effects but also the sensitivity of dissolution against variable attributes of a poorly water-soluble drug.

Study on Dissolution Profile of Commercial Glyburide Tablets

The dissolution profile (DP) of a glyburide containing tablet - Daonil (supplied by Hoechst, Germany and used as the reference sample) was compared with those obtained from thirty-four commercial glyburide tablets in this study. Dissolution tests were performed by using a USP XXIII aparatus-II (paddle type) at 75 rpm, and three buffer solutions of pH 7.8, 6.8 and 5.8, respectively, were used as the media. Released percentages of the active ingredient were meassured at 15, 30, 45, 60, 90 and 120 minutes. SUPAC* f2 factor proposed by FDA was applied to verify the similarity between the DP of Daonil and that of each investigated samples. Results indicated that 10 out of 34 case samples (29.4%) were similar in DPs to Daonil 1 in all of three media. In the meantime, three samples (8.8%) gave similar profiles as the control in two media of pH 7.8 and pH 5.8. It was also found that thirteen tested samples (38.2%) were similar in DPs to Daonil in a buffer solution of pH 5.8, but different in both media of pH 6.8 and pH 7.8. Furthermore, only one case sample gaved a completely different profile compared with that of Daonil no matter what pH of dissolution media was. Finally, statistics on the number of tested samples having similar DPs as Daonil in individual media are as follows: 13 in pH 7.8 (38.2%); 17 in pH 6.8 (50%); and 33 in pH 5.8 (97.1%).

A comparative study on the dissolution profiles of commercial hydrochlorothiazide tablets

Dissolution profiles (DPs) of Dichlotride tablet containing hydrochlorothiazide, supplied by Merck Sharp & Dohme, N.J., U.S.A. and used as the reference formulation in this study, were compared with those obtained from sixteen commercial tablets. Dissolution tests were performed by employing a USP XXIII apparatus-I (Basket type) at 100 rpm. Pure water, 0.1N HCl and pH 7.4 buffer were used as the studied media. Released percentages of the active ingredient were measured at 10, 20, 30, 45, 60 and 90 minutes, respectively. The factor f 2 of the FDA's SUPAC Guide was applied to the qualitative determination of 'similarity' between pairs of dissolution profiles of Dichlotride and those of each investigated formulations. Results indicated that 5 out of 16 tested samples (ca. 31.3%) were suited to Dichlotride in all of three media. In addition, three other samples (ca. 18.8% each) were similar to Dichlotride in both water and 0.1N HCl. Two tested formulations gave similar in-vitro release profiles to those of Dichlotride only in corresponding pure water or the pH 7.4 buffer solution (ca. 6.3% each), in other words, different in both of the other two media. The last six samples showed completely different profiles compared with that of Dichlotride no matter what medium was used. In summary, the number of tested samples showing similar DPs as Dichlotride in individual media were as follows: 8 in water (50%); 9 in 0.1N HCl (ca. 56.3%); and 6 in pH 7.4 buffer solution (37.5%).

3D printing of PVA capsular devices for modified drug delivery: design and in vitro dissolution studies

The fabrication through FDM 3D printing of hollow systems intended for oral drug delivery constitutes an attractive technology to change personalized medications in the compounding pharmacy. In this sense, this work studied the design and 3D printing of one compartment capsular devices filled of drugs that could require a delayed release mechanism. The optimization of printing parameters such as material flow rate and printing speed by means of simple gcode modifications, resulted critical to allow the production of PVA capsular devices in a single manufacturing process. In addition, the disintegration and dissolution studies of the obtained capsular device confirmed the existence of a delayed drug release compared to commercial hard-gelatin capsules. Furthermore, the use of sinkers in the dissolution tests resulted in similar dissolution profiles regardless the rotation speed. Finally, Gompertz and Weibull equations were the kinetic models that best fitted the experimental data corresponding to immediate release with lag time type profiles. Overall, this work provides insights to understand the effect of the printing parameters on the production of PVA capsular devices and suggests a simple design and single manufacturing process that can be adopted in the future compounding pharmacy.