Gastro-resistant Tablets Research Articles

Serratiopeptidase with diclofenac sodium for the management of post-operative pain and inflammation in a day care obstetric and gynaecological surgeries

Management of acute post-operative pain and swelling after the obstetric and gynaecological (OBG) surgeries is crucial part of patient care. Reduction or complete elimination of post-operative pain & swelling, without excessive sedation is the most preferred treatment strategy helping patient’s recovery in terms of rapid mobilization and return to independence. Serratiopeptidase a proteolytic enzyme used for its anti-inflammatory properties. Diclofenac Sodium is commonly used to treat the pain and swelling. This study aimed to evaluate the effectiveness and tolerability of the fixed dose combination (FDC) of Serratiopeptidase (10 mg) with Diclofenac Sodium (50 mg) gastro-resistant tablets in day care OBG surgery. This was a single centre, retrospective, observational data collection in real-life scenario. Data of adult women who had undergone day care OBG surgery and received a FDC of Serratiopeptidase (10 mg) with Diclofenac Sodium (50 mg) gastro-resistant tablets TID for period of 24 hours was retrieved and analysed. VAS (Visual Analogue Scale) data on post-operative pain at rest and pain on movement as well as post-operative swelling were analyzed in conjunction with monitoring for adverse events. Among 61 patient’s data included in the study, 40 (65.57%) had undergone Minimally Invasive Vaginal Hysterectomy (MIVH), 4 (6.56%) had MIVH with Bilateral Salpingo-oophorectomy, and 17 (27.87%) had other OBG surgeries. The average VAS scores for pain at rest (VAS), pain on movement (VAS) and swelling were significantly reduced compared to baseline at all-time points (p>0.001). Clinical global impression of efficacy and safety for 95% physician’s and 93.3% patients was good to very good. FDC was found to be well tolerated without any serious adverse reaction. The results of this clinical study confirms the effectiveness and tolerability of FDC of Serratiopeptidase and Diclofenac sodium in day care OBG surgeries in the early post-operative period.

Posaconazole gastro-resistant tablets for preventing invasive fungal disease after haematopoietic stem cell transplantation: a propensity-matched cohort study

ObjectivesTo evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations. MethodsA single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. ResultsThe prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09–5.50% vs. 7.69%; 95% CI, 4.60–10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively. DiscussionPatients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

Cerebrospinal fluid concentrations of posaconazole in paediatric leukaemia patients.

Little is known about the distribution of posaconazole in brain tissue and CSF. We therefore analysed trough concentrations of posaconazole in paediatric leukaemia patients in non-inflamed CSF. The study included paediatric patients <18 years of age with acute leukaemia in remission who underwent repeat therapeutic lumbar punctures as part of their anti-leukaemia treatment. CSF and blood were obtained 20-24 h after dosing, and posaconazole was measured by LC-MS/MS. Six patients (median age: 10 years; range, 6-14) with acute lymphatic (three) or acute myeloid (three) leukaemia were included who received posaconazole gastroresistant tablets at weight-banded doses (five) or the oral solution (one). In contrast to 14 control samples, posaconazole was detectable in all 11 samples of treated patients. CSF concentrations ranged from 8.3 to 42 ng/mL with a median CSF concentration of 13.6 ng/mL. Concurrent serum concentrations were between 965 and 5177 ng/mL with a median of 1716 ng/mL. Trough concentrations of posaconazole in the CSF after systemic administration were low but detectable in all subjects. Concurrent serum concentrations were in the target range for prophylaxis and treatment in 100% and 90%, respectively.

Stability Indicating RP-HPLC Method for the Estimation of Impurities in Esomeprazole Gastro-Resistant Tablets by AQbD Approach

Abstract Background: Esomeprazole (ESO) gastro-resistant tablets (40 mg) are sold under the brand name, Zosa, which effectively manages conditions associated with the overproduction of gastric acid, including peptic ulcer disease and Zollinger-Ellison syndrome. The present study quantifies impurities in esomeprazole using advanced analytical techniques known as analytical quality by design with high-performance liquid chromatography. Methods: Buffer selection (pH 7.6) and mobile phase composition (75:25 v/v) were optimized utilizing a YMC C18 column (150 mm × 4.6 mm; particle size, 3 μm) with a flow rate of 1.0 mL/min. The analyte was monitored with a UV/PDA detector at a wavelength of 280 nm. The stability-indicating nature of the method was confirmed based on forced degradation studies. The method validation was performed per ICH guidelines. Linearity, specificity, limit of detection, limit of quantification, precision, accuracy, solution stability, and robustness parameters were validated. Results: All validation parameters were within an acceptable range. Excellent linearity with correlation coefficient values &gt; 0.99 was achieved across the quantification limit. The solution stability study demonstrated no significant increase in percent impurity over a 24-h period. Analytical quality by design was instrumental in defining the design range for buffer pH and mobile phase composition, ensuring robust method performance. It was confirmed that 75% buffer solution, 25% acetonitrile, and pH 7.6 were the ideal conditions for determination of ESO impurities. Conclusion: The validated method provides a reliable tool for accurately quantifying impurities in ESO tablet formulations.

Single-Dose Crossover Comparative Bioavailability Study of Two Different Posaconazole 100 mg Gastro-Resistant Tablets Under Fasted and Fed Conditions in Healthy Volunteers.

This study aimed to compare the bioavailability of two different gastro-resistant oral tablet formulations of posaconazole under fasted and fed conditions and to evaluate a potential food effect on the bioavailability of each formulation. Healthy volunteers randomly assigned to receive a test product (Posagil® 100 mg gastro-resistant tablet) or reference product (Noxafil® 100 mg gastro-resistant tablet) were included in this single-center, randomized, four-period (days 1, 15, 29 and 43), four-sequence crossover comparative bioavailability study. Data on posaconazole plasma concentrations and related pharmacokinetic profile (the maximum observed plasma concentration [Cmax] from time 0 to the time of last observed quantifiable plasma concentration [AUC0-T] and from time zero to infinity [AUC0-∞]) were recorded to evaluate efficacy of the test product in relation to the reference product under both fasted and fed conditions, based on bioequivalence (T-fasted vs. R-fasted and T-fed vs. R-fed) and food effect (T-fasted vs. T-fed and R-fasted vs. R-fed) assessments. Safety was evaluated through assessment of adverse events (AEs), standard laboratory evaluations, and vital signs. The bioequivalence criteria were met under fed conditions (T-fed vs. R-fed: geometric LSMean ratios of Cmax, AUC0-T, and AUC0-∞ of posaconazole were 97.41%, 97.45%, and 97.08%, respectively; all within the range of 80% to 125%) but not under fasted conditions. There was a food effect on the reference product (R-fed vs. R-fasted: geometric LSMean ratios of Cmax, AUC0-T, and AUC0-∞ of posaconazole were 145.32%, 138.84%, and 138.46%, respectively) but not on the test product. No safety concerns were identified. Our findings suggest that the pharmacokinetic profile of Posagil® is similar to the pharmacokinetic profile of Noxafil®. The generic Posagil® seems to have similarly high bioavailability under fed and fasted conditions, offering a higher posaconazole exposure than the original Noxafil® in the fasted state. Hence, Posagil® may be considered a value-added generic product that offers adequate posaconazole exposure under fasted state and fed state, regardless of the concomitant high-fat meal intake.

Cost-effectiveness of weekly gastro-resistant risedronate 35mg, compared with weekly alendronate 70mg tablets, in the treatment of postmenopausal osteoporosis in Spain.

Aim: To estimate the cost-effectiveness of treating postmenopausal osteoporosis (PMO) with weekly gastro-resistant risedronate 35mg gastro-resistant tablets (RIS-GR), compared with weekly alendronate 70mg tablets (ALN) in Spain. Methods: A probabilistic analysis (second-order Monte Carlo simulation) was performed with a time horizon of 5years, from the perspective of the Spanish National Health System. The bone fracture probabilities were obtained from a cohort study of 3614 women from USA with PMO treated with RIS-GR (1807) or ALN (1807) (Thomasius, 2022). The pharmacological cost and the cost of fractures were obtained from Spanish sources (€ 2022). The utilities of patients with and without fracture (quality-adjusted life years [QALYs]) were obtained from the medical literature. Results: Compared with ALN, treatment with RIS-GR can avoid 79 fractures (between 75 and 82) every 1000 patients treated, and 0.0119 QALYs would be gained (between 0.0098 and 0.0140) per patient. Additionally, GR-RIS would generate a cost saving per patient of €1994 (€1437-2904) with a probability of 99.7%. The scenario analyses confirmed the stability of the base case results. Conclusion: According to this study, RIS-GR would be the dominant treatment (lower costs with QALY gain) compared with ALN.

S512 Effect of Esomeprazole Dual Release Gastro-Resistant Tablets in Patients With Refractory Gastroesophageal Reflux Disease in Comparison to Esomeprazole Tablets: A Double-Blind Randomized, Phase 3 Active-Controlled Trial

S512 Effect of Esomeprazole Dual Release Gastro-Resistant Tablets in Patients With Refractory Gastroesophageal Reflux Disease in Comparison to Esomeprazole Tablets: A Double-Blind Randomized, Phase 3 Active-Controlled Trial

P170 Life threatening hemoptysis in COVID-19 associated Pulmonary Aspergillosis (CAPA)

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveWe report a case of large pulmonary mycotic aneurysms with massive hemorrhage as an unusual complication of CAPA which required vascular radiological interventions along with appropriate antifungal treatment.Method and ResultsA 71-year-old female patient had COVID-19 and was admitted elsewhere and she received steroids, aspirin, antibiotics, and fluconazole. Cough, dyspnea, and hemoptysis started 3 weeks later which markedly worsened over 4 days, requiring emergency hospitalization due to shock, and she received a large number of packed RBCs. The chest CT scan revealed two large nodular opacities with central breakdown and CT pulmonary angiography revealed large mycotic aneurysms within the nodular opacities (Fig. 1).The important task at the moment of presentation was pulmonary artery embolization to arrest hemoptysis; which took precedence over the diagnosis and treatment of the likely infectious process. Both aneurysms were embolized using coils and vascular plugs resulting in their obliteration.Common causes of such nodules with central necrotic cavitation and formation of pseudoaneurysms are angioinvasive molds like Aspergillus and Mucorales. In the post-COVID-19 and post steroid setting in India, invasive Mucormycosis (IM) is thought to be more common than invasive Aspergillosis (IA). A mixed infection with these molds appears to be present in about 15% of the cases. Absence of DM or hyperglycemia was somewhat against a diagnosis of Mucormycosis. TB was considered less likely due to the imaging features and Nocardia was considered less likely due to the tempo of the illness and the severity of hemoptysis.Since the clinical distinction between Aspergillosis and Mucormycosis was not possible and posaconazole can be potentially useful for both, it was chosen for treatment in preference to voriconazole. Both amphotericin B and isavuconazole were in short supply at that time. Posaconazole was used for the patient intravenously followed by gastroresistant tablets. Expectorated sputum revealed narrow, septate, acute angle branching fungal hyphae. Therapeutic drug monitoring was used later to assure an adequate drug exposure. Serum galactomannan and BDG reports were received soon after and were 2.49 ODI (Optical density Index) and >523pg/ml respectively. The mold grew in culture as shown in and was identified by morphological features and by MALDI TOF MS as Aspergillus fumigatus (Fig. 2). Sensititre MIC to posaconazole was found to be 0.12 which is considered in the susceptible range.Despite these findings indicating IA, posaconazole was not replaced by voriconazole as IM could not be ruled out as part of a mixed infection. The patient showed clinical improvement, had no further hemoptysis, serum galactomannan turned negative and CT showed obliteration of the aneurysms.ConclusionPosaconazole and isavuconazole may indeed emerge as good contemporary choices over voriconazole for IA and over amphotericin B for IM.This case adds to the clinical experience of using medical treatment with posaconazole as the sole drug and not undertaking surgery in cases such as these, due to certain extenuating circumstances.

Comparative dissolution profiles of two anti-emetic delayed release dosage forms of doxylamine and pyridoxine: Xonvea® tablets vs. Cariban® capsules.

Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action. 10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed. In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine. At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.

Effect of soft beverages on the in vitro dissolution of gastro-resistant tablets containing low dose Acetylsalicylic acid

The need for additional fluids for easy absorption is typical for elderly patients and those with dysphagia. Most often, these patients take their medication with a glass of orange juice or another liquid instead of a glass of water. We conducted a dissolution test with gastro-resistant tablets acetylsalicylic acid where different kind of orange juice or soft drink wеre added to the release medium. As a control, release medium - buffers 1.2, 4.5 and 6.8 were used. The released aspirin was determined after HPLC analysis. The obtained data were fitted to different kinetic models. The results of the dissolution test in medium buffers with added different beverage showed results similar to those obtained in pure buffer, where it is used an artificial sweetener and different, when sugar or glucose-fructose syrup was used to sweeten the beverage. The most significant change was observed in the release kinetics of the active substance.To exclude the possibility that the other beverage ingredients or excipients used to make the tablets affect the release profile of acetylsalicylic acid, we conducted a beverage-like dissolution test. Instead of a original beverage, we used water and sugar syrup, in a concentration that is declared on the label of the original beverages. The results obtained confirm that different sugar concentrations alter the release profile of acetylsalicylic acid from gastro resistant tablets when they are taken with a glass of sugar-containing beverage instead of a glass of water.

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis.

ObjectivesTo investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses.Patients and methodsChildren from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function.ResultsOne hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7–17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%–83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6–11 years; and 86%–88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12–17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients.ConclusionsA starting dose of 300 mg OD in those aged 6–11 years and 400 mg OD in those aged 12–17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.

EPS3.10 Clinical pharmacokinetics and dose recommendations for posaconazole gastro-resistant tablets in children with cystic fibrosis

EPS3.10 Clinical pharmacokinetics and dose recommendations for posaconazole gastro-resistant tablets in children with cystic fibrosis

Preformulation and preliminary formulation studies of mesalazine gastro-resistant tablets

Preformulation and preliminary formulation studies of mesalazine gastro-resistant tablets

In vitro proportional investigation of different Pantoprazole sodium brands of gastro-resistant tablets

The present work is a comparative exploration of some of the physicochemical possessions like weight change, thickness, diameter, hardness, disintegration time, in vitro drug discharge, and analysis studies of various commercially available Pantoprazole sodium tablets (PST) containing 40 mg of drug. The hardness, loss on friability, dissolution test, disintegration test, and uniformity of drug content were evaluated. All the brands meet the requirements as per the pharmacopoeial standards. The dissolution profile study revealed that PST-1 was faster, while PST-2 was slower. The dissolution information was kinetically treated.

Comparative in vitro drug release examination of dissimilar brands of Rabeprazole sodium Gastro-Resistant Tablets

Comparative in vitro drug release examination of dissimilar brands of Rabeprazole sodium Gastro-Resistant Tablets

Determination of enantiomeric purity of esomeprazole by capillary electrophoresis

Abstract Proton pump inhibitors are the most effective agents used in gastric hyper-acidity-related disorders. Omeprazole is a benzimidazole-derivative compound with an asymmetric sulphur in its structure, which generates its chiral character. Esomeprazole (S-omeprazole) was the first proton pump inhibitor introduced as an enantiomerically pure compound in therapy, after the successful chiral switch of the racemic omeprazole. This work is aimed at performing a complementary study to an already published chiral separation method of omeprazole. As preliminary analysis, the electrophoretic behavior of omeprazole enantiomers and the possible mechanism of the chiral resolution was studied using different background electrolytes containing different β-cyclodextrin derivatives, as chiral selectors. The robustness of the chiral separation method was tested by applying a Plackett-Burman design. The method was validated according to current ICH guidelines and proved to be reliable, linear, precise and accurate for the determination of 0.2% R-omeprazole as chiral impurity in esomeprazole samples. The validated method was successfully used for the analysis of esomeprazole-containing gastro-resistant tablets. According to our results, valuable information on the mechanism of chiral separation of omeprazole was gained and the application area of the previously developed method was successfully enlarged. The presented rapid and cost-effective capillary electrophoresis method proved to be suitable for the determination of enantiomeric purity of esomeprazole from pharmaceutical preparations and could represent an alternative for the available compendial methods.

Oral Administration of Fucosylated Chondroitin Sulfate Oligomers in Gastro-Resistant Microcapsules Exhibits a Safe Antithrombotic Activity.

Fucosylated chondroitin sulfate (FCS) polysaccharide isolated from sea cucumber has potent anticoagulant activity. Based on its resistance to the enzymes present in vertebrates, it may serve as an anticoagulant and shows antithrombotic effects when delivered through gastro-resistant (GR) tablets. However, due to the multiple plasma targets of FCS polysaccharide in the coagulation pathway, bleeding can occur after its oral administration. In the current study, we used FCS oligomers, in particular a mixture of oligosaccharides having 6 to 18 saccharide units, as the active ingredient in GR microcapsules for oral anticoagulation. In a Caco-2 model, the FCS oligomers showed higher absorption than native FCS polysaccharides. Oral administration of FCS oligomer-GR microcapsules provided a dose-dependent, prolonged anticoagulant effect with a selective inhibition of the intrinsic coagulation pathway when compared with subcutaneous administration of FCS oligomers or oral administration of unformulated FCS oligomers or native FCS-GR microspheres. Continued oral administration of FCS oligomer-GR microcapsules did not result in the accumulation of oligosaccharides in the plasma. Venous thrombosis animal models demonstrated that FCS oligomers delivered via GR microcapsules produced a potent antithrombotic effect dependent on their anticoagulant properties in the plasma, while oral administration of unformulated FCS oligomers at the same dose exhibited a weaker antithrombotic effect than the formulated version. Oral administration of FCS oligomer-GR microcapsules resulted in no bleeding, while oral administration of native FCS-GR microcapsules resulted in bleeding (p < 0.05). Our present results suggest that a FCS oligomer-GR microcapsule formulation represents an effective and safe oral anticoagulant for potential clinical applications.

Comparison of the coating process and in vitro dissolution of 3 mm gastro-resistant minitablets and 5 mm gastro-resistant tablets with pantoprazole.

Minitablets are solid oral forms, which, due to their size (1-3 mm), may be easily swallowed by children. The administration of minitablets in a certain number of units allows for flexible dosing for a broad age group of paediatric patients, which is particularly important for modified-release drugs. In this study, enteric-coated minitablets (3 mm) with pantoprazole were developed and compared to conventional tablets (5 mm). Eudragit L 30D 55® and Acryl Eze II® films, which were 50 and 80 μm thick, respectively, were applied using two different fluid bed systems. The increase in the pantoprazole release rate occurred not only due to the application of a thinner film but also due to the reduction in the size of the core independent of the coating apparatus that was used. In contrast to minitablets, the thin film's thickness was insufficient for 5 mm tablets and a loss of gastro-resistance was observed. The insertion of minitablets into a hard gelatine capsule did not affect drug release from the minitablets under in vitro conditions.

PMS63 - COST-EFFECTIVENESS OF ACTONEL® 35 MG (RISEDRONATE) GASTRO-RESISTANT TABLETS FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS IN FRANCE

Actonel ® 35 mg (risedronate) gastro-resistant (GR risedronate) tablets are associated with improved persistence compared to common oral bisphosphonates, but are also slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. A previously validated Markov microsimulation model was used to estimate the lifetime cost (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with generic risedronate and alendronate. The model was populated with cost and epidemiological data from a French healthcare perspective. Pooled efficacy results for bisphosphonates derived from a previous NICE meta-analysis was used for all treatment options and persistence data (up to 3 years) were obtained from a large longitudinal study. Evaluation was done for high-risk women 60-80 years of age, with a bone mineral density (BMD) T-score ≤-2.5 and/or prevalent vertebral fractures. One-way and probabilistic sensitivity analyses were performed to test the robustness and uncertainty of the model results. In all of the simulated populations, GR risedronate was cost-effective compared to generic risedronate and alendronate at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤-2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to both generic risedronate and alendronate fall below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to generic risedronate and alendronate. This study provides the first economic results about Actonel ® 35 mg (risedronate) gastro-resistant, suggesting that it represents a cost-effective strategy compared with generic risedronate and alendronate for the treatment of postmenopausal women with osteoporosis in France.

Development of a dual extrusion printing technique for an acid- and thermo-labile drug

Over the last years fused deposition modeling has been increasingly considered as a game-changing technique for the preparation of individualized pharmaceutical products. Until now investigations have mainly focused on dosage forms loaded with very stable drugs or model substances. Going beyond this early stage of research, developers will also have to deal with more challenging active substances. In this work different printing designs for tablets containing the acid- and thermo-labile drug pantoprazole sodium were tested. Initial dual extrusion printing of a cellulose acetate phthalate coat and a tablet core of polyethylene glycol 6000 with 10% (m/m) pantoprazole sodium resulted in thermal degradation of pantoprazole at cellulose acetate phthalate printing temperatures of 141 °C. Therefore, different tablet designs were developed. The sectioning of the design of the tablet coat in a gastro-resistant cellulose acetate phthalate bottom part and an upper nearly insoluble polycaprolactone part printed at only 58 °C was suitable to prevent visible signs of thermal degradation. Dissolution testing indicated also no drug loss during dual extrusion printing. However, printed enteric tablets with shell thicknesses of 0.4 to 0.5 mm were not completely gastro-resistant. Drug release at intestinal pH values was delayed compared to uncoated cores. In conclusion, 3D-printing of gastro-resistant tablets containing thermo- and acid-labile drugs seems in principle possible. However, it remains an unsolved challenge to meet United States Pharmacopeia requirements.