NERDG 2026
Abstracts for STP Session 2 – Novel Oral Drug Delivery – Salon B
Presentation 1
Formulation development of extemporaneously prepared mucoadhesive in situ forming oral gels for phase 1 clinical studies.
Radha Kulkarni (1), Rajesh V. Lalla (2), Daniella Morales(3), Diane J. Burgess(1)
(1) School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA, (2)University of Connecticut, School of Dental Medicine, Farmington, CT 06030, USA, (3) Institute of Material Science, University of Connecticut, Storrs, CT 06269, USA
Purpose
Oral mucositis is a common side effect of chronic cancer therapy, which causes uncontrolled pain and lowers patient quality of life. Sprayable mucoadhesive in situ forming oral gels containing local anesthetic (Bupivacaine HCl) overcome the limitations of conventional pain control strategies via selected application to the affected area and increasing the drug residence time at the site of action. A mucoadhesive in situ forming oral gel was optimized from a pre-approved, Bupivacaine injection to accelerate its regulatory approval. Accordingly, the main objective of this research included understanding the impact of a marketed formulation on the critical quality attributes of mucoadhesive in situ forming oral gels.
Methods
A Pluronic based mucoadhesive in situ forming oral gel formulation was optimized using a pre-commercialized Bupivacaine injection, and sodium CMC as a mucoadhesive polymer (F1), and a control formulation was prepared using Bupivacaine HCl powder and the same composition of Pluronics and sodium CMC (F2) as F1. The impact of the marketed formulation on the critical quality attributes was evaluated via i) mucoadhesion; ii) rheology; iii) in vitro release; iv) gelation temperature; and v) liquid crystalline structure determination (SAXS).
Results
No impact was observed on sprayability and pH for F1 and F2. Both formulations showed similar gel consolidation and crossover temperatures for oscillatory temperature sweeps. However, the presence of sodium chloride in F1 leads to a cubic liquid crystalline structure, in contrast to the hexagonal arrangement of F2. Consequently, these differences resulted in a higher gelation temperature and mucoadhesion for F1. Additionally, F1 showed a significantly faster drug release compared to F2 due to the faster diffusivity of the drug through the continuous, interconnected water channels of the cubic phase compared to the closed cylindrical structure of the hexagonal arrangements.
Conclusions
A reproducible method has been successfully developed for extemporaneous preparation of mucoadhesive in situ forming oral gels to provide a more patient-centric approach towards pain management for cancer patients suffering from oral mucositis. The presence of sodium chloride ions can impact the liquid crystalline structure of mucoadhesive in situ forming oral gels, leading to differences in their critical quality attributes.
Keywords
mucoadhesion, personalized medicine, in situ forming gels, rheology, oral cavity, in vitro release, liquid crystalline structure, first in human clinical studies.
Abstracts for STP Session 2 – Novel Oral Drug Delivery – Salon B
Presentation 1
Formulation development of extemporaneously prepared mucoadhesive in situ forming oral gels for phase 1 clinical studies.
Radha Kulkarni (1), Rajesh V. Lalla (2), Daniella Morales(3), Diane J. Burgess(1)
(1) School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA, (2)University of Connecticut, School of Dental Medicine, Farmington, CT 06030, USA, (3) Institute of Material Science, University of Connecticut, Storrs, CT 06269, USA
Purpose
Oral mucositis is a common side effect of chronic cancer therapy, which causes uncontrolled pain and lowers patient quality of life. Sprayable mucoadhesive in situ forming oral gels containing local anesthetic (Bupivacaine HCl) overcome the limitations of conventional pain control strategies via selected application to the affected area and increasing the drug residence time at the site of action. A mucoadhesive in situ forming oral gel was optimized from a pre-approved, Bupivacaine injection to accelerate its regulatory approval. Accordingly, the main objective of this research included understanding the impact of a marketed formulation on the critical quality attributes of mucoadhesive in situ forming oral gels.
Methods
A Pluronic based mucoadhesive in situ forming oral gel formulation was optimized using a pre-commercialized Bupivacaine injection, and sodium CMC as a mucoadhesive polymer (F1), and a control formulation was prepared using Bupivacaine HCl powder and the same composition of Pluronics and sodium CMC (F2) as F1. The impact of the marketed formulation on the critical quality attributes was evaluated via i) mucoadhesion; ii) rheology; iii) in vitro release; iv) gelation temperature; and v) liquid crystalline structure determination (SAXS).
Results
No impact was observed on sprayability and pH for F1 and F2. Both formulations showed similar gel consolidation and crossover temperatures for oscillatory temperature sweeps. However, the presence of sodium chloride in F1 leads to a cubic liquid crystalline structure, in contrast to the hexagonal arrangement of F2. Consequently, these differences resulted in a higher gelation temperature and mucoadhesion for F1. Additionally, F1 showed a significantly faster drug release compared to F2 due to the faster diffusivity of the drug through the continuous, interconnected water channels of the cubic phase compared to the closed cylindrical structure of the hexagonal arrangements.
Conclusions
A reproducible method has been successfully developed for extemporaneous preparation of mucoadhesive in situ forming oral gels to provide a more patient-centric approach towards pain management for cancer patients suffering from oral mucositis. The presence of sodium chloride ions can impact the liquid crystalline structure of mucoadhesive in situ forming oral gels, leading to differences in their critical quality attributes.
Keywords
mucoadhesion, personalized medicine, in situ forming gels, rheology, oral cavity, in vitro release, liquid crystalline structure, first in human clinical studies.
Presentation 2
Nanoliposomal Formulation of lipophilic Gemcitabine derivative for the Treatment of naïve and drug resistance brain cancer
Bhoomi Dholariya, Himaxi Patel, Ketan Patel
College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11432
Glioblastoma is the most aggressive and deadliest type of brain tumor with very limited therapeutic options. Poor brain permeability of anticancer molecules is one of the major causes of high mortality rate. Temozolomide (TMZ) is the first-line treatment for patients with Glioblastoma (GBM) but development of resistant lead to relapse and treatment failure in more than 50% of patients. After screening over 25 potential candidates (so far unexplored for GBM), we have identified a lipophilic derivative of gemcitabine as promising candidate for naïve and temozolomide-resistant GBM. The purpose of this study is to develop and characterize a long-circulating nanoliposomal formulation of gemcitabine elaidate (GE-GemNano).
Nanoliposomal formulation of GE was developed using dual centrifugal nanomilling techniques as solvent-free, scale-up feasible approach. Different batches were prepared with varying types of phospholipids (DOPC, DPPC, and Sphingomyelin) and drug loading method (active and passive loading of GE). Batches were optimized for particle size, zeta potential, drug entrapment efficiency and stability. Cytotoxicity, clonogenic, multicellular 3D spheroid growth assay and apoptosis assays of GE and GemNano were carried out using U87 and temozolomide-resistant U87 (TR-U87) cells. BBB permeability was estimated using bEnd.3 monolayer and compared with swissADME and Gatroplus model.
Modified hydration method with nanomilling was found to be superior to conventional liposomal formulation techniques for enhancing GE loading. Batches containing DOPC as core phospholipid and prepared via active loading method exhibited 120nm±0.2 size, -18.6±0.3 and >98% entrapment efficiency. Optimized exhibited uniform particle distribution, with no signs of aggregation or drug crystallization in Cryo-TEM analysis. BBB permeability revealed a clinically relevant concentration in receiver compartment. IC₅₀ of GE/DMSO and GemNano was found to be ~35-42nM and ~3-5µM in U87 and TR-U87 GBM cells, respectively. The growth of multicellular tumor spheroids was inhibited by 61.9% compared to the control group at the end of 10 days of alternate-day treatment. Efficacy evaluation of GemNano in patient-derived GBM cells is currently ongoing.
A high-throughput comprehensive screening revealed the potential of GE for the treatment of naïve and drug-resistant brain cancer. GemNano could be a potential nanotherapeutics for the treatment of GBM alone and in combination with temozolamide and bevacizumab.
Keywords:
Glioblastoma, Gemcitabine Elaidate, Liposomes, Nanomilling, Temozolomine resistance
Presentation 2
Nanoliposomal Formulation of lipophilic Gemcitabine derivative for the Treatment of naïve and drug resistance brain cancer
Bhoomi Dholariya, Himaxi Patel, Ketan Patel
College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11432
Glioblastoma is the most aggressive and deadliest type of brain tumor with very limited therapeutic options. Poor brain permeability of anticancer molecules is one of the major causes of high mortality rate. Temozolomide (TMZ) is the first-line treatment for patients with Glioblastoma (GBM) but development of resistant lead to relapse and treatment failure in more than 50% of patients. After screening over 25 potential candidates (so far unexplored for GBM), we have identified a lipophilic derivative of gemcitabine as promising candidate for naïve and temozolomide-resistant GBM. The purpose of this study is to develop and characterize a long-circulating nanoliposomal formulation of gemcitabine elaidate (GE-GemNano).
Nanoliposomal formulation of GE was developed using dual centrifugal nanomilling techniques as solvent-free, scale-up feasible approach. Different batches were prepared with varying types of phospholipids (DOPC, DPPC, and Sphingomyelin) and drug loading method (active and passive loading of GE). Batches were optimized for particle size, zeta potential, drug entrapment efficiency and stability. Cytotoxicity, clonogenic, multicellular 3D spheroid growth assay and apoptosis assays of GE and GemNano were carried out using U87 and temozolomide-resistant U87 (TR-U87) cells. BBB permeability was estimated using bEnd.3 monolayer and compared with swissADME and Gatroplus model.
Modified hydration method with nanomilling was found to be superior to conventional liposomal formulation techniques for enhancing GE loading. Batches containing DOPC as core phospholipid and prepared via active loading method exhibited 120nm±0.2 size, -18.6±0.3 and >98% entrapment efficiency. Optimized exhibited uniform particle distribution, with no signs of aggregation or drug crystallization in Cryo-TEM analysis. BBB permeability revealed a clinically relevant concentration in receiver compartment. IC₅₀ of GE/DMSO and GemNano was found to be ~35-42nM and ~3-5µM in U87 and TR-U87 GBM cells, respectively. The growth of multicellular tumor spheroids was inhibited by 61.9% compared to the control group at the end of 10 days of alternate-day treatment. Efficacy evaluation of GemNano in patient-derived GBM cells is currently ongoing.
A high-throughput comprehensive screening revealed the potential of GE for the treatment of naïve and drug-resistant brain cancer. GemNano could be a potential nanotherapeutics for the treatment of GBM alone and in combination with temozolamide and bevacizumab.
Keywords:
Glioblastoma, Gemcitabine Elaidate, Liposomes, Nanomilling, Temozolomine resistance
Presentation 3
A Novel Oral Excipient for Solid Dosage Forms – Formulation Development, Characterization, and IVIVC Prediction
Zia Uddin Masum(1), Nitin Kumar Swarnakar(2), Ming Ji(2), Vivek Gupta(1)
(1) Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, 8000 Utopia Parkway, Queens, NY 11439, USA, (2) BASF, 500 White Plains Rd, Tarrytown, NY 10591
Purpose:
Sucrose Acetate Isobutyrate (SAIB) is an FDA-approved polyfunctional excipient that can improve solubility, mucoadhesion, amorphous dispersions, and ultimately bioavailability for BCS Class II-IV drugs. In this study, we explore the feasibility of developing an oral solid dosage form of the BCS Class II drug Quetiapine (QTP) using SAIB and assess its clinical performance using GastroPlus®-enabled IVIVC simulation.
Methods:
QTP granules with 21.74% or 13.04% SAIB, and 43.48% drug loading were prepared by solvent evaporation (QD tablets) or wet granulation (QE tablets). The flowability, physicochemical characteristics, and tabletability of the granules were evaluated. The USP II method was followed for dissolution testing. The scalability of both QTP tablet formulations was evaluated using STYLone®. Based on in-vitro dissolution and corresponding clinical data from the innovator product, Seroquel, an IVIVC model was developed using Gastroplus 9.9 to forecast clinical performance.
Results:
The granulation with SAIB significantly improved QTP’s solubility (>63%). Granules from QD22% and QE13% were analyzed using DSC, XRD, SEM, and TGA. For both processes, the SAIB formulations were determined to be more amorphous than the pure drug. >80% cumulative drug release showed that both QD22% and QE13% formulations released the payload within 1 hour, and this release profile remained unchanged in tablets undergoing accelerated stability testing. When compressed with STYLone, QD22% demonstrated acceptable scalability and exhibited a similar dissolution profile to that of lab-scale tablets. Validation results from the developed IVIVC model showed prediction errors <15% for both Cmax and the Area Under the Curve (AUC), demonstrating the appropriateness of our method for predicting human QTP plasma concentrations. Using the verified IVIVC model, we simulated the in-vitro dissolution results of the QD22% formulation and demonstrated >85% absorption of the released drug in the small intestine. The simulated clinical PK profile also demonstrated significantly better systemic absorption with SAIB-enabled QTP tablets (100 mg) compared to the innovator product: greater Cmax (0.190 µg/mL vs 0.158 µg/mL for innovator), and AUC (1.628 µg·h/mL vs 1.568 µg·h/mL for innovator), achieving a total absorption of 98.7%.
Conclusion
SAIB is a feasible and potent novel excipient for oral solid dosage forms of BCS Class 2 drugs.
Keywords:
SAIB, QTP, STYLone, GastroPlus®, IVIVC, FDA, Cmax, AUC
Presentation 4
Data-Driven Formulation of Solid Oral Dosage Forms: Integrating Computational Modeling with Experimental Validation Using ZoomLab
Suman Choudhary(1), Zia U Masum(1), Sravani Ravula(1), Nitin K Swarnakar(2), Vivek Gupta(1)
(1)Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences St. John’s University, Queens, NY 11439, USA (2) BASF Corporation, Pharma Solutions, 500 White Plains Road, Tarrytown, NY-10591, USA
The development of robust solid oral dosage forms traditionally relies on empirical, trial-and-error approaches that are resource-intensive and prone to failure during scale-up. AI-powered predictive software enables a rational, data-driven approach to identifying and selecting excipients and compositions, thereby achieving target performance attributes and streamlining the development process. In this study, ZoomLab®, a formulation design platform developed by BASF, was leveraged to develop immediate-release (IR) ibuprofen tablets using a direct compression (DC) approach. Ibuprofen was selected as the model drug due to its high dose requirements and inherent challenges in flowability and compressibility, making it an ideal candidate for evaluating the capabilities of computational formulation design. ZoomLab® was used to screen multiple co-processed excipients based on predicted processability scores, from which five co-processed excipients, FlowLac® 90, MicroceLac® 100, CombiLac®, Kollitab™ DC 87L, and Ludipress®, were deemed suitable for direct compression at a 40% drug load. Experimental batches were prepared using the DC method, followed by characterization of granules for flow properties and tablet properties, including hardness, friability, disintegration, and dissolution behavior. Thermal and solid-state characterization was performed using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). A comparative performance assessment was conducted against marketed IR formulations (Advil® and Motrin®) to evaluate bioequivalence potential based on f1 and f2 values. Among the evaluated compositions, the Kollitab DC 87L-based formulation demonstrated optimal tablet hardness (~95N), friability <1%, rapid disintegration, and granule flow properties with dissolution profiles (>85% release in 45 minutes) that closely matched the marketed products, meeting USP criteria. Further evaluations included three-month stability studies at 25±2 °C /60±5% RH, which confirmed the formulation’s physicochemical stability. The biocompatibility and safety of the formulation were assessed using Caco-2 cell assays, demonstrating an acceptable toxicity profile. An in-vitro in-vivo correlation (IVIVC) model was developed and validated using GastroPlus® (v9.9) in accordance with F0DA guidelines. The model successfully predicted pharmacokinetic parameters, including AUC, Tmax, and regional gastrointestinal absorption of ibuprofen. Overall, the study demonstrates the feasibility and utility of ZoomLab® as a predictive, data-driven tool for rational excipient selection and formulation design.
Keywords:
Oral tablets; IVIVC; immediate-release; Ibuprofen
