The Burgess lab is focused on formulation science, drug delivery and manufacturing science of complex parenterals as well as implantable biosensors for metabolic monitoring. Research efforts cover the basic science of interfacial chemistry, the application of this in pre-formulation and formulation development, the development of novel drug delivery systems, and the in vitro and in vivo testing of these drug delivery systems including investigation of biopharmaceutics and pharmacodynamics. Our research is applied to solving problems with respect to drug and gene delivery and focuses on microsphere, nanoparticle, liposome, emulsion, hydrogel and in situ forming delivery systems. In the area of implantable insulin delivery devices and biosensors, efforts are focused on biocompatible coatings to prevent the foreign body reaction that would otherwise result in catheter blockage and eventual failure, or loss of sensor sensitivity and eventual sensor failure, respectively. In the area of pharmaceutical manufacturing a continuous manufacturing platform for complex parenterals has been developed with full online process analytical technology, that can achieve robust product quality.

Major contributions include: development of novel microcapsule dosage forms; development of “real-time” and accelerated performance tests for complex parenteral dosage forms and development of IVIVCs for these complex dosage forms; modeling of the pharmacokinetics of proteins implanted in microsphere dosage forms; correlation of interfacial properties with emulsion and nanoparticle stability; development of a novel composite coating for implantable devices that has been shown to prevent the foreign body response in animal models in excess of 6 months; development of a method that allows long-term intracellular and intranuclear tracking of gene therapeutics and gene delivery vectors; design of safe, efficient and stable non-viral gene delivery systems; application of quality-by-design principles to nanoparticles and liposomes; and development of novel manufacturing methods for liposomes, polymer micelles, LNPs (lipid nanoparticles) and emulsions, including the development of continuous manufacturing methods with inline process analytical technology for these complex parenterals.


Enabling the rational development of long-acting contraceptive hormonal intrauterine implants:

Ashwin Abhang:

The past few years have witnessed a change in women’s contraceptive choices with an increasing number of women using hormonal intrauterine systems (IUSs) to provide long-term contraception (3-8 years). Despite the first levonorgestrel (LNG) IUS (Mirena®) being introduced in 2000, currently, there are only four LNG-IUS products approved by the U.S. Food and Drug Administration (FDA) and there are no LNG-IUS generic products. The difficulty in developing generic LNG-IUSs stems from their ultra-long-acting nature, structural complexity (monolithic matrix-reservoir type drug-device combination), manufacturing challenges, lack of a clear understanding of excipient characteristics, locally-acting nature, and an incomplete understanding of drug release mechanisms. The dearth of generic LNG-IUS limits access to affordable LNG-IUSs. The objectives of the present research are to identify and investigate the impact of critical material attributes and processing parameters, to investigate the role of excipients on product performance; to elucidate drug release mechanisms of LNG-IUSs, and develop real-time and accelerated in vitro release testing methods in order to improve product understanding and enable the rational development of their generics. Furthermore, we are also utilizing the image-analytics tool and AI-based release simulation algorithms to provide a deeper understanding of the LNG-IUS microstructure to facilitate image-based release prediction.


Liposomal nanoparticles produced via continuous manufacturing as reference standard materials:

Luke Burroughs:

Following the recent success of lipid nanoparticles (LNPs) for the delivery of mRNA COVID-19 vaccines, there is an anticipated increase in demand for such lipid-based therapeutics and vaccines. Accordingly, there is incentive to develop suitable reference materials. Such materials would provide significant benefits to regulatory agencies and industry for product development, quality control, and technology transfer. Our laboratory has developed a continuous manufacturing platform that can produce monodisperse liposomes and LNPs with precise control over particle size. The objective of this work is to investigate long term stability and characterization of candidate liposomal reference materials under different storage conditions.


Assessing microstructural critical quality attributes in PLGA microspheres:

Ruifeng Wang:

The distribution of the active pharmaceutical ingredient (API) within polymer-based controlled release drug products is a critical quality attribute (CQA). It is crucial for the development of such products, to be able to accurately characterize phase distributions in these products to evaluate performance and microstructure (Q3) equivalence. Polymer, API, and porosity distributions in poly(lactic-co-glycolic acid) (PLGA) microspheres were characterized using a combination of focused ion beam scanning electron microscopy (FIB-SEM) and quantitative artificial intelligence (AI) image analytics. Through in-depth investigations of nine different microsphere formulations, microstructural CQAs were identified including the abundance, domain size, and distribution of the API, the polymer, and the microporosity. 3D models, digitally transformed from the FIB-SEM images, were reconstructed to predict controlled drug release numerically. Agreement between the in vitro release experiments and the predictions validated the image-based release modelling method.


Spray-freeze-dried Mucoadhesive Solid Dispersions for the Delivery of Peptides/Proteins:

Radha Kulkarni :

Most proteins and peptides are prone to physicochemical degradation and other instabilities when formulated in a liquid state. On the other hand, solid-state formulations of protein/peptides are less prone to denaturation and precipitation during manufacturing and storage. Accordingly, different drying techniques are used to manufacture protein/peptide formulations with improved shelf-life for systemic absorption via different routes of administration such as oral and pulmonary.

Spray drying is a single-step, continuous, and scalable method of drying and particle engineering of protein/peptide formulations. Though spray drying is a simple technique with short processing times, it is unsuitable for materials sensitive to high temperatures. In addition, the yield of spray-dried products is typically between 50-70%. Freeze-drying is a commonly used drying technique for protein/peptides without the need for elevated temperature. However, the long processing times, complex processes, and high maintenance costs are some of the limitations of freeze-drying. In the current research, we are using spray-freeze-drying which is an effective technique combining the traditional approaches of spray-drying and freeze-drying and is recently gaining attention. In spray-freeze-drying, a liquid solution containing the drug, polymer, and stabilizers is aspirated through an atomizer using a cryogenic fluid such as liquid nitrogen. Following this, the frozen particles are sublimed under sub-atmospheric pressure. The particle characteristics and drug release from spray-freeze-dried microparticles may be impacted by the spray-freezing process parameters and thus there is a need to control process and formulation parameters, in order to develop a robust drug product with optimal performance. The present research utilizes spray-freeze-drying to develop mucoadhesive protein/peptide microparticulate solid dispersions for controlled drug (protein/peptide) delivery via the oral route. We are utilizing a quality-by-design (QbD) approach to develop the spray-freeze-dried mucoadhesive protein/peptide microparticulate solid dispersions. This will facilitate an understanding of the impact of the spray-freeze-drying process and formulation parameters on the quality attributes and performance of the mucoadhesive protein/peptide microparticulate solid dispersions.


Mucoadhesive Thermosensitive In Situ Forming Gel Containing Local Anesthetics for Oral Mucositis Pain Control:

Radha Kulkarni:

Oral mucositis is a common side effect of radiation and chemotherapy, and it is characterized by mild to moderate inflammation, sores and uncontrolled pain. The current first-line therapy for oral mucositis pain control is unsatisfactory as it results in only a short duration of modest pain relief. To overcome the limitations of existing therapies, a mucoadhesive in situ forming gel containing Bupivacaine is proposed to achieve a prolonged duration of pain control. The formulation is sprayable at room temperature so it can be selectively sprayed on the affected mucosal area to minimize side effects and it contains mucoadhesive polymers to enhance the mucosal contact time. Developing mucoadhesive in situ forming formulations to prolong pain relief is challenging due to their complex physicochemical properties and unique requirements for oral mucosa application. The objective of this study is to develop a mucoadhesive in situ forming gel formulation with enhanced efficacy. We are investigating the effect of different mucoadhesive polymers, salts, and physiological considerations in the development and optimization of the formulation. Furthermore, we are developing suitable assessment techniques for the formulation. The physicochemical properties of the gels are characterized, including gelation behavior, ex vivo mucoadhesion, rheological properties, in vitro drug release, and sprayability.


Development of in vitro-in vivo correlations for long-acting injectable suspensions:

Nilesh Malavia:

Long-acting injectable (LAI) aqueous suspensions achieve extended drug release over a duration of weeks to months via slow dissolution of drug crystals with low solubility. There have been around ten LAI aqueous suspensions approved by the FDA to date and there are no generic equivalents for most of them. This may be largely due to the complex formulation development as well as the challenges in establishment of in vitro-in vivo correlation (IVIVC) for these products. Level A IVIVCs, using animal models, have been proven feasible for complex long-acting microsphere formulations with multiphasic release characteristics. Accordingly, it may be possible to develop IVIVCs for LAI aqueous drug suspensions since their release characteristics are relatively simple with only a drug dissolution phase.


In vivo characterization of persersis and compositionally equivalent formulations:

Xiaoyi Wang:

Perseris is a subcutaneous extended-release risperidone in situ forming implant (suspension) indicated for the treatment of adult schizophrenia. Owing to the release rate controlling polymer poly(lactide-co-glycolide) (PLGA), one injection of Perseris can deliver risperidone for one month, which significantly reduces the administration frequency and improves patient compliance. The PLGA and drug used in Perseris was previously identified through reverse engineering and two compositionally equivalent formulations (F-1 and F-2) showing similar in vitro drug release were developed. The in vivo pharmacokinetic (PK) profiles, drug absorption rate, phase separation rate, macro appearance, weight loss as well as the water uptake of the solidified drug depots at different time points were investigated and compared with the in vitro release data as well as with dog and human in vivo data available in literature. This work provides a comprehensive in vitro/in vivo understanding of Perseris and the developed compositionally equivalent formulations, which will be beneficial for future development of generic as well as novel PLGA in situ forming implant products.

Impact of API CQAs on In Situ Forming Implants and Understanding In Vivo and In Vitro Performance Differences

McKenzie Roy: