Applications of synthetic and semisynthetic polymers (Kollidon K25, Kollidon K90 and Hydroksyethylocellulose) as carriers of ketoprofen in solid oral prolonged release dosage forms. The impact of selected non-ionic surfactants (Tween 80 and Rofam 70) on the release kinetic

Aims After oral administration, naproxen generates several side-effects related to stomach malfunction. Undoubtedly, the enteric dosage forms with naproxen can be considered as safer. Moreover, since it has been evidenced that development and growth of colorectal cancer is related to the presence of cyclooxygenase, naproxen is investigated in terms of the tumor prevention. The aim of the present work was to formulate and evaluate the properties of novel naproxen-loaded macrobeads, made on the basis of low-acyl gellan gum and its blends with carrageenans, guar gum, cellulose sulfate, and dextran sulfates. Method Seven formulations were prepared by ionotropic gelation. The morphology of the dried beads was evaluated by scanning electron microscopy. The next step focused on Raman spectroscopy and thermal analysis of naproxen, polymers, and the beads. Next, the swelling behavior was examined in three acceptor fluids at pH = 1.2; 4.5, and 7.4. The beads were evaluated regarding naproxen content and encapsulation efficiency. The last stage of the work concerned the drug release studies. Results Addition of any other polysaccharide than gellan resulted in flattening of the beads upon drying. Differential scanning calorimetry confirmed the crystalline form of naproxen. Raman spectra showed that no apparent interactions occurred. In the acidic environment, all the beads revealed the tendency to absorb water. The beads swelled to the greatest extent at pH = 4.5. Naproxen was released from the beads at a varied rate. At pH = 7.4, the most prolonged release was observed for the beads containing carrageenans. Conclusions We have proved that blending of gellan with various polysaccharides can change the pH-dependent properties of the beads loaded with naproxen. We believe that the information enclosed in the paper will be of particular importance regarding the development and characteristics of novel oral dosage forms based on natural polymers.

Download Full-text

Effect of Molecular Composition of Head Group and Temperature on Micellar Properties of Ionic Surfactants with C12 Alkyl Chain

Molecules ◽

10.3390/molecules24030651 ◽

2019 ◽

Vol 24 (3) ◽

pp. 651 ◽

Cited By ~ 2

Author(s):

Jarmila Oremusová ◽

Zuzana Vitková ◽

Anton Vitko ◽

Marián Tárník ◽

Eva Miklovičová ◽

...

Keyword(s):

Thermodynamic Parameters ◽

Dosage Forms ◽

Sodium Sulphate ◽

Ionic Surfactants ◽

Head Group ◽

Optimal Dosage ◽

Trimethylammonium Chloride ◽

Counterion Binding ◽

Micellar Properties ◽

The Impact

The paper analyses influences of the temperature and hydrophilic groups on micellar properties of ionic surfactants with 12-carbonic hydrophobic chains. The aim is to assess the impact of hydrophilic groups and temperature on thermodynamic parameters and micellization. This knowledge is indispensable for the formulation of new dosage forms. The method uses conductometric measurements. The following hydrophilic groups are analyzed: trimethylammonium bromide, trimethylammonium chloride, ethyldimethylammonium bromide, didodecyldimethylammonium bromide, pyridinium chloride, benzyldimethyl-ammonium chloride, methylephedrinium bromide, cis and trans-[(2-benzyloxy)-cyclohexyl-methyl]-N, N-dimethylammonium bromide, sodium sulphate and lithium sulphate. Except for a few cases, there is a good agreement between values of critical micellar concentrations (CMC) and critical vesicle concentration (CVC) obtained here and those which were obtained by other authors and/or by other physicochemical methods. Values of the CMC are compared with respect to the molar masses of hydrophilic groups. It was found that CMC values increased non-linearly with increasing system temperature. The degrees of counterion binding and thermodynamic parameters, like the standard molar Gibbs energy, enthalpy and entropy of micellization are determined and discussed in detail. The results obtained will be incorporated into in silico processes of modeling and design of optimal dosage forms, a current interdisciplinary research focus of the team.

Download Full-text

The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles

Pharmaceutics ◽

10.3390/pharmaceutics12050455 ◽

2020 ◽

Vol 12 (5) ◽

pp. 455

Author(s):

Emilia Szymańska ◽

Katarzyna Woś-Latosi ◽

Julia Jacyna ◽

Magdalena Dąbrowska ◽

Joanna Potaś ◽

...

Keyword(s):

Drug Release ◽

Polymer Matrix ◽

Drug Loading ◽

Water Soluble ◽

Dissolution Behavior ◽

Complex Nature ◽

Prolonged Release ◽

Scanning Calorimetry ◽

Burst Effect ◽

The Impact

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

Download Full-text

Embedded 3D Printing of Novel Bespoke Soft Dosage Form Concept for Pediatrics

Pharmaceutics ◽

10.3390/pharmaceutics11120630 ◽

2019 ◽

Vol 11 (12) ◽

pp. 630 ◽

Cited By ~ 14

Author(s):

Katarzyna Rycerz ◽

Krzysztof Adam Stepien ◽

Marta Czapiewska ◽

Basel T. Arafat ◽

Rober Habashy ◽

...

Keyword(s):

Dosage Form ◽

Drug Loading ◽

Three Dimensional ◽

Dosage Forms ◽

Dose Titration ◽

Step Method ◽

Needle Size ◽

Model Drug ◽

Semi Solid ◽

The Impact

Embedded three-dimensional printing (e-3DP) is an emerging method for additive manufacturing where semi-solid materials are extruded within a solidifying liquid matrix. Here, we present the first example of employing e-3DP in the pharmaceutical field and demonstrate the fabrication of bespoke chewable dosage forms with dual drug loading for potential use in pediatrics. LegoTM-like chewable bricks made of edible soft material (gelatin-based matrix) were produced by directly extruding novel printing patterns of model drug ink (embedded phase) into a liquid gelatin-based matrix (embedding phase) at an elevated temperature (70 °C) to then solidify at room temperature. Dose titration of the two model drugs (paracetamol and ibuprofen) was possible by using specially designed printing patterns of the embedded phase to produce varying doses. A linearity [R2 = 0.9804 (paracetamol) and 0.9976 (ibuprofen)] was achieved between percentage of completion of printing patterns and achieved doses using a multi-step method. The impact of embedded phase rheological behavior, the printing speed and the needle size of the embedded phase were examined. Owning to their appearance, modular nature, ease of personalizing dose and geometry, and tailoring and potential inclusion of various materials, this new dosage form concept holds a substantial promise for novel dosage forms in pediatrics.

Download Full-text

The SLC16A11 Risk Haplotype for Type 2 Diabetes (T2D) Is Associated to Differentiated Responses in Weight Loss, and Glucose Metabolism After Treatments to Prevent T2D

Current Developments in Nutrition ◽

10.1093/cdn/nzaa058_033 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1275-1275

Author(s):

Magdalena Sevilla ◽

Donaji Gomez-Velasco ◽

Ivette Cruz-Bautista ◽

Laura Lazaro-Carrera ◽

Paloma Almeda-Valdes ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Area Under The Curve ◽

Postprandial Glucose ◽

Tolerance Test ◽

Oral Glucose ◽

Prolonged Release ◽

Risk Haplotype ◽

The Impact

Abstract Objectives A haplotype in SLC16A11 is associated with decreased insulin action, and risk for type 2 diabetes (T2D) in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D. Methods We recruited subjects with at least one prediabetes criteria according to the American Diabetes Association, and body mass index 25–45 kg/m2. Subjects were randomized in two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids and 15% protein sources + physical activity (>150 min medium intensity per week), or LSI + metformin (750 mg prolonged release twice a day). Interventions were prescribed by standardized dietitians. The goal was to achieve >3% weight loss. We evaluated the early treatment response in a follow-up period of 12 weeks with intermediate visits each 3 weeks to reinforce knowledge and treatment goals. Evaluations (baseline and post-treatment) included an oral glucose tolerance test (OGTT), and dual-energy X-ray absorptiometry. Adherence to treatment was measured trough electronic recordings. Participants were genotyped for the risk allele rs13342232. Researchers remained blinded to the genotype results. The effects of the risk haplotype were evaluated with linear and logistic regressions adjusted by age, sex, and baseline body fat %. Results We evaluated 61 subjects, 30 carriers, and 31 non-carriers. Most of participants (57%) achieved ≥3% weight loss. The LSI + metformin treatment increased in carriers, 2 times OR 3 IC95% (1.07 – 8.6) (P = 0.04) the probability to reach the ≥3% weight loss goal compared with LSI and non-carriers. In the same treatment, carriers had a greater decrease in the total and incremental area under the curve of insulin in the OGTT IC95% (−1.75 −0.11) (P = 0.02) compared with non-carriers and LSI. Carriers also had higher decrease in postprandial glucose compared with non-carriers regardless of treatment −12.63 + 30.38 vs 0.71 30.24 (P = 0.02). Conclusions After 12 weeks of treatment, carriers with prediabetes showed a higher probability achieve weight loss and to improve insulin secretion with metformin. Regardless of the treatment, carriers were prone to improve postprandial glucose. Funding Sources Miguel Aleman Medical Research Award.

Download Full-text

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Polymers ◽

10.3390/polym12091872 ◽

2020 ◽

Vol 12 (9) ◽

pp. 1872 ◽

Cited By ~ 4

Author(s):

Rishi Thakkar ◽

Amit Raviraj Pillai ◽

Jiaxiang Zhang ◽

Yu Zhang ◽

Vineet Kulkarni ◽

...

Keyword(s):

Drug Release ◽

Hydroxypropyl Methylcellulose ◽

Amorphous State ◽

Dosage Forms ◽

Water Soluble ◽

Patient Specific ◽

3 Dimensional ◽

Fused Deposition ◽

3D Printed ◽

The Impact

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

Download Full-text