Search Results (14)

An enteric coating plays a crucial role in preventing the disintegration of pharmaceutical dosage forms in the stomach. This is particularly important for drugs unstable at an acidic pH or designed to act in the small intestine. While conventional synthetic polymers have been widely used for enteric coatings, there is growing interest in exploring naturally derived proteins as an alternative. This study focused on two natural polymers: soy protein and whey protein isolates, first by determining the gastro-resistance properties of films prepared from these proteins. Then, appropriate casting solutions were developed to create polymeric films, and their resistance to acidic pH was evaluated using disintegration tests. Second, crate drug pellets coated with the most effective protein-based film were previously prepared, and their performance was assessed using the USP apparatus I (basket). The results demonstrated that the coated pellets (SA and SAG) exhibited excellent gastro-resistance properties. Specifically, the percentage release of the coated pellets met the USP criteria: less than 10% release in the first 2 h under acidic conditions, followed by at least 80% release within 45 min in the buffer phase. In contrast, uncoated pellets showed immediate release, with over 69% of the dye released during the initial 2 h. Notably, the SA and SAG-coated pellets demonstrated remarkable resistance to acidic pH, releasing only 1% and approximately 2% of the dye faster than uncoated pellets. These findings highlight the potential of SA and SAG coating films for efficient delayed release or enteric coating applications. Full article

Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product. Full article

The aim of this study is to compare three different dissolution methods to assess the drug release from oral lyophilisates, based on interpolyelectrolyte complexes (IPECs). IPECs were prepared by mixing solutions of a linear polymer, Eudragit^® EPO, with a polymer with a cross-linked structure, Noveon^® AA-1 or Carbopol^® 10 Ultrez (in ratios of 1:2 and 1:1, respectively). Metformin or metronidazole were used as model drugs to achieve a systemic or local effect. A comparative assessment of the drug release kinetics was carried out using artificial saliva and three different set-ups: a paddle stirrer (USP apparatus 2), a flow cell (USP apparatus 4) and a Franz diffusion cell. The results demonstrated that oral lyophilisates disintegrated within 1 min. In the case of metformin, the drug release was completed in about 90 min independently of the set-up. The static conditions in the Franz diffusion cell and USP apparatus 2 permitted the aggregation of the IPEC; therefore, the release profiles show a significant difference compared to the USP apparatus 4. Full article

Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5–25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion—surface utilization factor—were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing. Full article

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. Full article

Measurements of external mass-transfer coefficients for dissolution have been made with benzoic acid tablets with a diameter of 13 mm and approximately 3 mm thick, using two different dissolution systems. One system has been a beaker with a platform for the tablet and either 80 mL or 120 mL of water, with three different types of stirrers, and the other has been a USP dissolution apparatus 2 (paddle) with either 200 mL or 900 mL water. Various stirring speeds have also been used in the different pieces of equipment. The same mass-transfer coefficient may potentially be obtained from the same tablet by adjusting the operating conditions in the two different devices. The ranges of the external mass-transfer coefficients measured in both devices overlapped significantly, with the range being 0.193–4.48 × 10⁻⁵ m s⁻¹ in the beaker and stirrer system and 0.222–3.45 × 10⁻⁵ m s⁻¹ in the USP dissolution apparatus 2. Dimensional analysis of the results, using Sherwood and Reynolds numbers, shows that the Ranz–Marshall correlation provides a lower bound for estimates of the Sherwood numbers measured experimentally. Calculations of time constants for mass transfer suggest that mass transfer may be a rate-limiting step for dissolution and food digestion under some circumstances. The range of mass-transfer coefficients measured here is representative of other measurements from the literature, and the use of the Ranz–Marshall correlation supports the suggestion that this range of values should be generally expected in most situations. Full article

The transdermal route of administration of drug substances allows clinicians to obtain a therapeutic effect bypassing the gastrointestinal tract, where the active substance could be inactivated. The hormonal substance used in the study-corticotropin (ACTH)-shows systemic effects. Therefore, the study of the effect of the type of ointment base and drug concentration on the release rate and also permeation rate in in vivo simulated conditions may be a valuable source of information for clinical trials to effectively optimize corticotropin treatment. This goal was achieved by preparation ointment formulation selecting the appropriate ointment base and determining the effect of ACTH concentration on the release and permeation studies of the ACTH. Semi-solid preparations containing ACTH were prepared using Unguator CITO e/s. The release study of ACTH was tested using a modified USP apparatus 2 with Enhancer cells. The permeation study was conducted with vertical Franz cells. Rheograms of hydrogels were made with the use of a universal rotational rheometer. The dependence of the amount of released and permeated hormone on the ointment concentration was found. Based on the test of ACTH release from semi-solid formulations and evaluation of rheological parameters, it was found that glycerol ointment is the most favourable base for ACTH. The ACTH release and permeation process depends on both viscosity and ACTH concentration. The higher the hormone concentration, the higher the amount of released ACTH but it reduces the amount of ACTH penetrating through porcine skin. Full article

Corticotropin (ACTH, previously an adrenocorticotropic hormone) is used in the diagnosis and treatment of pituitary gland disorders, adrenal cortex disorders, and other diseases, including autoimmune polymyositis, systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. So far, the ointment dosage form containing ACTH for use on the skin is unknown. Therefore, it seems appropriate to develop a semi-solid formulation with corticotropin. Emulsion ointments were prepared using an Unguator based on the cream base Lekobaza^® containing corticotropin in different concentrations, and then the physical and chemical parameters of the ointment formulations, such as pH, spreadability, rheological properties, and texture analysis, were evaluated. In addition, a USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the selected formulations. All the ointments obtained were characterized by good spreadability and viscosity. An analysis of the ointment texture was performed and the dependence of the tested parameters on the ACTH content in the ointment was demonstrated. Examination of the structure of the ointment showed that a high concentration of ACTH increases the hardness and adhesiveness of the ointment. In turn, it adversely affects the cohesiveness and elasticity of the ointments tested. The results of the release study showed that ACTH is released the fastest from the formulation with the lowest concentration, while the slowest from the ointment with the highest concentration of ACTH. Full article

In this study a novel type of in vitro–in vivo correlation (IVIVC) is proposed: The correlation of the in vitro parent drug dissolution data with the in vivo pharmacokinetic data of drug’s metabolite after the oral administration of the parent drug. The pharmacokinetic data for the parent drug diltiazem (DTZ) and its desacetyl diltiazem metabolite (DTZM) were obtained from an in vivo study performed in 19 healthy volunteers. The pharmacokinetics of the parent drug and its metabolite followed a pseudomono-compartmental model and deconvolution of the DTZ or DTZM plasma concentration profiles was performed with a Wagner–Nelson-type equation. The calculated in vivo absorption fractions were correlated with the in vitro DTZ dissolution data obtained with USP 2 apparatus. A linear IVIVC was obtained for both DTZ and DTZM, with a better correlation observed for the case of the metabolite. This type of correlation of the in vitro data of the parent compound with the in vivo data of the metabolite could be useful for the development of drugs with active metabolites and prodrugs. Full article

The impact of formulation and process variables on the in-vitro release of prednisone from a multiple-unit pellet system was investigated. Box-Behnken Response Surface Methodology (RSM) was used to generate multivariate experiments. The extrusion-spheronization method was used to produce pellets and dissolution studies were performed using United States Pharmacopoeia (USP) Apparatus 2 as described in USP XXIV. Analysis of dissolution test samples was performed using a reversed-phase high-performance liquid chromatography (RP-HPLC) method. Four formulation and process variables viz., microcrystalline cellulose concentration, sodium starch glycolate concentration, spheronization time and extrusion speed were investigated and drug release, aspect ratio and yield were monitored for the trained artificial neural networks (ANN). To achieve accurate prediction, data generated from experimentation were used to train a multi-layer perceptron (MLP) using back propagation (BP) and the Broyden-Fletcher-Goldfarb-Shanno (BFGS) 57 training algorithm until a satisfactory value of root mean square error (RMSE) was observed. The study revealed that the in-vitro release profile of prednisone was significantly impacted by microcrystalline cellulose concentration and sodium starch glycolate concentration. Increasing microcrystalline cellulose concentration retarded dissolution rate whereas increasing sodium starch glycolate concentration improved dissolution rate. Spheronization time and extrusion speed had minimal impact on prednisone release but had a significant impact on extrudate and pellet quality. This work demonstrated that RSM can be successfully used concurrently with ANN for dosage form manufacture to permit the exploration of experimental regions that are omitted when using RSM alone. Full article

A potentiometric electronic tongue was applied to study the release of valsartan from pharmaceutical formulations, i.e., minitablets uncoated and coated with Eudragit E. Special attention was paid to evaluate the influence of medium temperature and composition, as well as to compare the performances of the sensor arrays working in various hydrodynamic conditions. The drug dissolution profiles registered with the ion-sensitive electrodes were compared with standard dissolution tests performed with USP Apparatus 2 (paddle). Moreover, the signal changes of all sensors were processed by principal component analysis to visualize the release modifications, related to the presence of the coating agent. Finally, the importance and influence of the experimental conditions on the results obtained using potentiometric sensor arrays were discussed. Full article

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. Full article

This study describes the in vitro/ex vivo buccal release of chlorhexidine (CHX) from nine mucoadhesive aqueous gels, as well as their physicochemical and mucoadhesive properties: CHX was present at a constant 1% w/v concentration in the chemical form of digluconate salt. The mucoadhesive/gel forming materials were carboxymethyl- (CMC), hydroxypropylmethyl- (HPMC) and hydroxypropyl- (HPC) cellulose, alone (3% w/w) or in binary mixtures (5% w/w); gels were tested for their mucoadhesion using the mucin method at 1, 2 and 3% w/w concentrations. CHX release from different formulations was assessed using a USP method and newly developed apparatus, combining release/permeation process in which porcine mucosa was placed in a Franz cell. The combination of HPMC or HPC with CMC showed slower drug release when compared to each of the individual polymers. All the systems proved suitable for CHX buccal delivery, being able to guarantee both prolonged release and reduced transmucosal permeation. Gels were compared for the release of previously studied tablets that contained Carbopol and HPMC, alone or in mixture. An accurate selection and combination of the materials allow the design of different pharmaceutical forms suitable for different purposes, by simply modifying the formulation compositions. Full article

In the present work a new indomethacin (IND) self-nanoemulsifying drug delivery formulation (SNEDDF) have been prepared to enhance its dissolution which in turn could provide a better chance for IND oral absorption. IND SNEDDF have been prepared using different concentrations of castor oil as a solvent for IND, Cremophor RH 40 (Cr-40) as surfactant and Capmul MCM-C8 (Ca-8) as co-surfactant. Droplets size and turbidity of IND SNEDDFs were measured. Dissolution profile of IND SNEDDFs filled in gelatin capsules was determined by using USP apparatus 2. Ternary phase diagram was constructed to identify the self-nanoemulsifying region after evaluation of IND SNEDDFs by the visual observation. The IND SNEDDFs were thermally characterized using differential scanning calorimetry (DSC) to ensure the compatibility among its ingredients. The present study revealed that the SNEDDFs increased IND dissolution rate and has the potential to enhance its bioavailability without interaction or incompatibility between the ingredients. Full article