Search Results (72)

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Background: Pharmaceutical compounding remains a predominantly manual process with limited innovation, particularly in non-sterile applications. This study explores the implementation of an automated compounding platform based on 3D printing to enhance precision, efficiency, and adaptability in pediatric corticosteroid formulations. Methods: Personalized hydrocortisone dosage forms were prepared in a hospital pharmacy setting using a proprietary excipient base and standardized procedures, including automated dosing and syringe heating when required. Three dosage forms—3.2 mg gel tablets, 2.8 mg water-free troches, and 1.2 mg orodispersible films (ODFs)—were selected to demonstrate the platform’s versatility and to address pediatric needs for varying strengths and dosage types. All products were prepared using a reproducible semi-solid extrusion (SSE)-based workflow with the consistent API-excipient blending and automated deposition. Results: Analytical testing confirmed that all formulations met pharmacopeial criteria for mass and content uniformity. The ODF and troche forms achieved rapid drug release, exceeding 75% within 5 min, while the gel tablet showed a slower release profile, reaching 86% by 60 min. Additionally, in-process homogeneity testing across syringe printing cycles confirmed the consistent API distribution. Conclusions: The results support the feasibility of integrating automated compounding technologies into pharmacy workflows. Such systems can improve accuracy, minimize variability, and streamline the production of customized pediatric medications, particularly for drugs with poor palatability or narrow therapeutic windows. Overall, this study highlights the potential of automation to modernize non-sterile compounding, and to better support individualized therapy. Full article

The main aim of this study was to develop a diclofenac-loaded, orodispersible formulation prepared by double-needle electrospinning. For the use of two needles, one above the other, a new needle holder was designed and 3D printed. During the optimization of the drug-free PVP carrier, the effect of the polymer concentration on the morphology and average fiber diameter was investigated. Electrospinning was possible for solutions with a PVP concentration between 7.5 and 15 w/w%. Too low viscosity led to smooth-surfaced nanoparticles, since electrospraying occurred. The optimal material properties and process parameters were used to prepare drug-loaded nanofibers. The morphology, crystallinity, chemical interactions, encapsulation efficiency, drug distribution, in vitro disintegration, in vitro dissolution, cytocompatibility, and 6-month stability were tested. According to the results, the electrospun formulation was an amorphous solid dispersion with excellent encapsulation efficiency. The drug distribution was homogeneous within the nanofiber matrix. The disintegration was completed in about 5 s in artificial saliva and about 41 s on an artificial tongue. The dissolution in artificial saliva was complete within 10 min. Overall, a promising formulation was developed with rapid disintegration, immediate drug release, and good stability. Additionally, a new in vitro dissolution method (“AS-to-FaSSGF”) was developed to obtain a bigger picture of drug dissolution throughout the gastrointestinal tract. Full article

Background: Angiotensin-converting enzyme inhibitors, such as enalapril, are foundational in treating pediatric heart failure. However, they are often administered off-label to young children using extemporaneous formulations. This study, conducted as part of the EU-funded Labeling of Enalapril from Neonates up to Adolescents (LENA) project, aimed to evaluate the acceptability and palatability of an age-appropriate enalapril orodispersible minitablet (ODMT). These factors are critical for ensuring adherence, efficacy, and safety in pediatric patients. Methods: An 8-week trial was conducted in children with heart failure caused by dilated cardiomyopathy or congenital heart disease. Enalapril ODMTs (0.25 mg or 1.0 mg) were dose-titrated and administered to 38 children aged 0–6 months and 22 children aged 6 months to 6 years. This study aimed to assess its acceptability and palatability, key factors contributing to adherence, and therefore, efficacy and safety. Results: Across all 169 assessments in 38 children aged 0–6 months and 22 aged 6 months to 6 years, complete or partial swallowability was observed, and the acceptability rate was 100%. There were no cases of choking, inhalation/coughing, or spitting out. A favorable or neutral rating was observed in 96% of palatability assessments based on observations of facial expressions. Acceptability and palatability were higher in subjects aged 6 months–6 years than 0–6 months, with no significant influence from repeated administration. Conclusions: Enalapril ODMTs are widely accepted and well-tolerated among young children, including neonates, with heart failure. These findings suggest that ODMTs are a suitable and effective method for administering pediatric medicinal products. Full article

Background/Objectives: Cilnidipine (CIL) is a calcium channel blocker that exhibits low bioavailability (~13%) due to poor aqueous solubility and extensive pre-systemic gut wall metabolism. The current study aimed to enhance the oral bioavailability of CIL by formulation of polymeric spherical agglomerates (CILSAs)-based orodispersible tablets (ODTs). Methods: Eight different batches of CILSAs were prepared by a crystallo-co-agglomeration technique using different proportions of hydrophilic polymers like hydroxy propyl methyl cellulose E50, polyvinyl pyrrolidone K30, or polyethylene glycol (PEG) 6000 as carriers. Fourier transform infrared spectroscopy (FTIR) of CILSAs proved the chemical integrity of CIL in SAs, while scanning electron microscopy revealed the spherical shape of CILSAs. Results: Differential scanning calorimetry and powder X-ray diffraction studies confirmed that CIL was rendered more amorphous in CILSAs. CILSAs displayed good flow behavior, high percentage yield, and high drug loads. The batch F4 composed of PEG 6000 emerged as the optimized batch as it displayed high percentage dissolution efficiency (57.01 ± 0.01%), which was significantly greater (p < 0.001) compared to CIL (26.27 ± 0.06%). The optimized formulation of CILSAs was directly compressed into ODTs that were rendered porous by vacuum drying. The optimized formulation of porous ODTs (T3) displayed low friability (0.28 ± 0.03%), short disintegration time (6.26 ± 0.29 s), and quicker dissolution (94.16 ± 1.41% in 60 min) as compared to marketed tablet Cildipin^® 10 mg (85 ± 2.3%). Conclusions: Thus, porous ODTs of CILSAs can rapidly release the drug, bypass gut metabolism, enhance oral bioavailability, and improve CIL’s therapeutic effectiveness for angina and hypertension. Full article

Orodispersible thin film (ODF) is an innovative dosage form that allows for adjustable dosing and improved patient compliance. It is administered by mouth, where it dissolves, making it suitable for children. Objectives: The aim of the study was to develop and characterize an optimal ODF formulation containing equivalent hydrocortisone at 0.5 mg/cm² using the solvent-casting method. A stability-indicating assay for the simultaneous quantification of hydrocortisone and hydrocortisone 21-hemissucinate (HMS) was developed. ODFs were characterized by organoleptic properties and by testing for uniformity of mass, content, stability, thickness, and dissolution. Results: When optimized, ODF is thin, flexible, and transparent, making it suitable for production in hospital pharmacies using standard equipment. In contrast to the water-insoluble hydrocortisone, the HMS-loaded cast gel successfully satisfied the tests, including content uniformity. Disintegration appeared acceptable as compared to the commercial grade ondansetron ODF (Setofilm^®). The physicochemical stability of the active ingredients (i.e., HMS, hydrocortisone) contained in the ODF at 0.5 mg/cm² is demonstrated for at least 84 days at 23 °C. Conclusion: The ODF formulated with the water-soluble hydrocortisone prodrug HMS allows accurate drug level to be achieved, thus opening up new opportunities for use in pediatric patients. Full article

Background: Trihexyphenidyl (THP) has been widely used for over three decades as pediatric pharmacotherapy in patients affected by segmental and generalized dystonia. In order to achieve effective and safe pharmacotherapy for this population, new formulations are needed. Objective: The aim of this work is the development of trihexyphenidyl orodispersible minitablets (ODMTs) for pediatric use. Methods: Six different excipients were tested as diluents. The properties of powder mixtures were evaluated before direct compression and pharmacotechnical tests were performed on the final formulation. The determination of the API content, uniformity of dosage, and physicochemical stability studies were analyzed by an HPLC-UV method. Results: The developed ODMTs met pharmacopeia specifications for content, hardness, friability, disintegration, and dissolution tests. The physicochemical stability study performed over 18 months shows that API content remains within 90.0–110.0% at least for this period. Conclusions: These ODMTs will allow efficient, safe, and high-quality pharmacotherapy. Full article

Background/Objectives: This project aims to provide valuable insights into the formulation of orodispersible films (ODFs) for the delivery of PROTAC ARV-110. The primary objective of this drug delivery formulation is to enhance the solubility of PROTAC ARV-110, which faces significant challenges due to the low solubility of this active pharmaceutical ingredient, as it belongs to a molecular class that is considered to exceed the “Rule of Five”. Methods: We employed the concept of developing a rapidly disintegrating ODF to enhance the solubility of PROTAC ARV-110, utilizing polyvinyl alcohol as the polymer of choice. Given the high thermal stability of ARV-110, the PROTAC was subjected to two primary ODF manufacturing techniques: Hot melt extrusion (HME) and solvent casting. To establish the HME method, pre-screening through vacuum compression molding was performed. The films were characterized based on their disintegration in artificial saliva, drug release in a physiological environment, and mechanical strength. Results: All formulations demonstrated enhanced solubility of ARV-110, achieving exceptional results in terms of disintegration times and resistance to applied stress. Conclusions: The findings from the experiments outlined herein establish a solid foundation for the successful production of orodispersible films for the delivery of PROTACs. Full article

Background/Objectives: Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. Methods: This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. Results: A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. Conclusions: This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population. Full article

Background: The angiotensin-converting enzyme inhibitor (ACEI) enalapril is often administered to infants and young children with heart failure (HF) in various dosing regimens and formulations not adapted for their age. Methods: This prospective, two-center, open-label 8-week study evaluated an age-appropriate formulation of orodispersible minitablets (ODMTs) of enalapril (0.25 mg and 1 mg) in children aged 0 to 6 years with HF due to congenital heart disease. An age/weight-based dosing schedule was followed. Measures of echocardiographic parameters, blood pressure, heart rate, modified Ross score, and biochemistry were obtained over the 8-week period. The following two groups were assessed: ACEI-naïve and ACEI-pretreated patients. Results: In total, 53 children (age range of 0.05 to 4.8 years) were enrolled and 29 were ACEI-naïve. The average enalapril dose was 0.098 mg/kg (0.06–0.17 mg/kg) in the naïve group and 0.15 mg/kg (0.07–0.3 mg/kg) in pretreated patients. After 8 weeks, the modified Ross score and left ventricular diastolic dimension (LVD) z-score showed a significant decrease in both groups (p < 0.005). During 8 weeks follow-up, there were no difference in the z-scores for the systolic blood pressure (p = 0.071) or heart rate (p = 0.146). Conclusions: Pediatric patients treated with ODMTs of enalapril for 8 weeks had favorable improvements in LVD and HF symptoms. Full article

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further. Full article

Vitamin D3 is a crucial fat-soluble pro-hormone essential for bolstering bone health and fortifying immune responses within the human body. Orodispersible films (ODFs) serve as a noteworthy formulation strategically designed to enhance the rapid dissolution of vitamin D, thereby facilitating efficient absorption in patients. This innovative approach not only streamlines the assimilation process but also plays a pivotal role in optimizing patient compliance and therapeutic outcomes. The judicious utilization of such advancements underscores a paradigm shift in clinical strategies aimed at harnessing the full potential of vitamin D for improved patient well-being. This study aims to examine the vitamin D3 ODF structure using spectroscopic techniques to analyze interactions with excipients like mannitol. Fourier-transform infrared spectroscopy (FTIR) and ultraviolet–visible (UV–Vis) spectroscopy were utilized to assess molecular composition, intermolecular bonding, and vitamin D3 stability. Understanding these interactions is essential for optimizing ODF formulation, ensuring stability, enhancing bioavailability, and facilitating efficient production. Furthermore, this study involves a translational approach to interpreting chemical properties to develop an administration protocol for ODFs, aiming to maximize absorption and minimize waste. In conclusion, understanding the characterized chemical properties is pivotal for translating them into effective self-administration modalities for Vitamin D films. Full article

Rhinacanthins, derived from Rhinacanthus nasutus, widely used in traditional medicine, exhibit antifungal, anticancer, antiviral, antibacterial, and antiplatelet aggregation effects. Recently, their anti-diabetic activity was confirmed, which makes them an interesting natural alternative in the therapy of the early stage of diabetes mellitus. The aim of this study was to demonstrate the possibility of formulating orodispersible tablets (ODTs) and orodispersible films (ODFs) containing rhinacanthin-rich extract (RRE). Tablets with 50 mg or 100 mg of RRE were produced by direct compression. ODFs were manufactured by casting of Lycoat RS 720 or polyvinyl alcohol solution with RRE and additional excipients. The mechanical properties and disintegration times of the prepared formulations were studied. The effectiveness of taste masking was analyzed with an electronic tongue system. Six months simplified stability studies were performed in conditions complying to ICH guidelines. Appropriate friability of ODTs was achieved, despite low tensile strength (0.45–0.62 MPa). All prepared ODFs successfully met the acceptance criteria regarding Young’s modulus, tensile strength, and elongation at break. The observed variations in their mechanical properties were dependent on the type and quantity of polymers and plasticizers used. Disintegration time of ODTs ranged from 38.7 s to 54.2 s, while for ODFs from 24.2 to 40 s in the pharmacopoeial apparatus. Analyses made with the electronic tongue showed the significant taste-masking effect in both formulations. The addition of sucralose as a sweetener and menthol with mint flavor as a taste-masking agent was sufficient to mask an RRE’s taste in the case of ODTs and ODFs. Stability studies of ODTs packed in the PVC/Alu blisters showed a decrease in the RRE content below 90% after 6 months. However, ODFs with PVA were physicochemically stable for 6 months while being stored in Alu/Alu sachets. Our study proved for the first time the possibility of the formulation of orodispersible dosage forms with RRE, characterized by good mechanical properties, disintegration time, and appropriate taste masking. Full article

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages. This study investigated Vacuum Compression Molding (VCM) as a solvent-free manufacturing method for the preparation of flexible-dose pediatric orodispersible films. The experimental approach focused on selecting the appropriate plasticizer and ratios of the active pharmaceutical ingredient, diclofenac sodium, followed by the study of their impacts on the mechanical properties, disintegration time, and drug release profile of the ODFs. Additional investigations were performed to obtain insights regarding the solid-state properties. The ODFs obtained by VCM displayed adequate quality in terms of their critical characteristics. Therefore, this proof-of-concept study shows how VCM could be utilized as a standalone method for the production of small-scale ODFs, enabling the customization of doses to meet the individual needs of pediatric patients. Full article

Cefdinir (CEF) is a semi-synthetic third-generation broad-spectrum oral cephalosporin that exhibits poor solubility at lower pH values. Considering this, pH-modulated CEF solid dispersions (ASDs) were produced by solvent evaporation method employing various hydrophilic carriers and alkalizers. Among different carriers, ASDs produced using PEG 6000 with meglumine as alkalizer were found to significantly increase (p < 0.005) the drug solubility (4.50 ± 0.32 mg/mL) in pH 1.2. Fourier transform infrared spectrophotometry confirmed chemical integrity of CEF while differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) indicated CEF was reduced to an amorphous state in ASD8. Antimicrobial assay performed by well diffusion method against Staphylococcus aureus (MTCC96) and Escherichia coli (MTCC118) demonstrated significantly superior (p < 0.001) efficacy of CEFSD compared to CEF. The porous orodispersible tablets (ODTs) of ASD8 (batch F5) were developed by incorporating ammonium bicarbonate as a subliming agent by direct compression, followed by vacuum drying displayed quick disintegration (27.11 ± 1.96 s) that met compendial norms and near-complete dissolution (93.85 ± 1.27%) in 30 min. The ODTs of ASD8 appear to be a promising platform to mitigate the pH-dependent solubility and dissolution issues associated with CEF in challenging physiological pH conditions prevalent in stomach. Thus, ODTs of ASD8 are likely to effectively manage various infections and avoid development of drug-resistant strains, thereby improving the curing rates. Full article