Development of antihyperlipidemic drug loaded β-CD-based microparticulate carrier systems: tuning and optimization

ABSTRACT

Our study focused on developing and optimizing β-CD-based microparticulate carrier systems to enhance lovastatin’s solubility and systemic availability (LST). Specifically, we designed solid dispersions, inclusion complexes, and hydrogel microparticles as carrier systems. Fourier-transform infrared spectroscopy (FTIR) studies were conducted to ensure drug–polymer interactions and ingredient compatibility. Additionally, we investigated the physical state, thermal stability, topology, internal morphology, and particle size using techniques such as powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta size, and zeta potential. Our results confirmed the formation of compatible and thermally stable networks within an acceptable particle size range. The entrapment efficiency and product yield fell within 83.50–88.50% and 87–90.50%, respectively. Notably, all developed formulations exhibited a significant increase in solubility at pH 6.8 compared to LST commercial Tablets, as indicated by the regression coefficient (R2) for the release of LST following first-order kinetics. We compared LST commercial tablets with our optimized formulations (SD3 and HA3) for pharmacokinetic evaluation. SD3 demonstrated a Cmax of 63.64 µg/ml, an AUC o-t of 555.79 µg/ml.h, and a half-life (t1/2) of 7.3 h. In contrast, HA3 exhibited superior pharmacokinetic parameters with a Cmax of 93.543 µg/ml, an AUC o-t of 1154.35 µg/ml.h, and a t1/2 of 10.33 h. These results indicate the efficient release of LST from the developed carrier systems, supported by increased Cmax and lower tmax values. Furthermore, biochemical and histopathological studies on our optimized formulations confirmed their biocompatibility. Our findings demonstrate our developed β-CD-based microparticulate carrier systems’ effectiveness in enhancing lovastatin’s solubility, systemic availability, and biocompatibility.

GRAPHICAL ABSTRACT

KEYWORDS:

• Lovastatin
• solubility
• microparticulate carrier systems
• pharmacokinetic evaluation

Acknowledgments

The authors extend their appreciation to the Researchers Supporting Project number (RSPD2024R620), King Saud University, Riyadh, Saudi Arabia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Notes on contributors

Zameer Ul Hassan Shah

Dr. Zameer Ul Hassan Shah is currently working as managing director of Citi Pharmaceuticals Lahore. He got his Ph. D. degree in Pharmaceutics from College of Pharmacy, University of Sargoha, Pakistan. He has more than 20 years of experience relevant to drug product development, clinical trials, TQM, production and R & D with his name.

Sajid Bashir

Prof. Dr. Sajid Bashir has done Ph. D. (Pharmaceutics) from the University of the Punjab, Lahore, before that, he completed M. Phil (Pharmaceutics) University of the Punjab, Lahore, Pakistan. His area of expertiese include Biopharmaceutics, Pharmaceutics, Formulation Development and industrial pharmacy. He served as Dean Faculty of Pharmacy, University of Sargodha. He has supervised many M. Phil and Ph. D. students.

Rai Muhammad Sarfraz

Dr. Rai Muhammad Sarfraz has completed his Ph. D in Pharmaceutics from Islamia University of Bahawalpur, Punjab Pakistan in 2016. Currently he is working as Assistant Professor of Pharmacy in University of Sargodha, Pakistan. He has published more than 90 research articles with impact factor more than 200. He has supervised 7 Ph. D students and 25 M. Phil students till now. His area of interests are hydrogels, Solubility enhancement and polymers.

Asif Mahmood

Dr. Asif Mahmood is currently working as Assistant Professor, Department of Pharmacy, University of Chakwal. He has completed his Doctorate degree from The Islamia University of Bahawalpur. He has performed research in the field of polymerization, solubility enhancement and drug product development by forming hydrogel micro-particles, solid dispersions, inclusion complexes, or dispersible tablets and hydrogels etc. He has published more than 83 research articles in well reputed international impact factor journals. He has presented his work in variety of national as well as international forum. He has more than 06 years of teaching experience with his name. He was awarded research productivity award twice by The University of Lahore, Punjab, Pakistan.

Umaira Rehman

Dr. Umaira Rehman completed her Ph. D. in Pharmaceutics from university of Sargodha, Sargodha, Pakistan in 2021. She is currently serving as Associate Professor at Lahore College of Pharmaceutical Sciences since 2008. She has supervised and co-supervised various post-graduate students. Following her Ph. D. she authored and co-authored different research articles in international journals and having 24 publications. She has expertise in development of various drug delivery systems.

Hira Ijaz

Dr. Hira Ijaz have done Ph. D. (Pharmaceutics) in November 2020. I have served as Lecturer at Department of Pharmacy, University of Agriculture Faisalabad as assistant Professor in Department of Pharmacy, The University of Faisalabad. Currently, Working as Assistant Professor Pharmaceutics at Department of Pharmaceutical Sciences, Pak-Austria Fachhochschule: Institute of Applied Science and Technology. I have received Young Scientist Award in 2022. My fields of interest include polymerization, solubility enhancement and drug product development by designing hydrogel micro-particles, microneedle patches, microgels, solid dispersions, inclusion complexes, or dispersible tablets and hydrogels etc. My current projects include development of various carrier systems from natural polymers for anticancer drug delivery.

Mohamed M. Salem

Dr. Mohamed M. Salem research interests lie at the intersection of neurology and pharmacology, driven by a fascination with the human nervous system. Based at Huazhong University of Science and Technology, I explore the potential of pharmacological solutions for neurological conditions. My work focuses on identifying novel therapeutic targets and developing innovative drug discovery strategies in this field. Through collaborative efforts, I aim to contribute advancements that improve patient care.

Sayed H. Auda

Prof. Dr. Sayed Hassan Mohammed Auda, Ph. D. of Pharmaceutical Sciences, pharmaceutics and industrial pharmacy department., Al-Azhar University. He studded his doctorate at Martin Luther University, Germany in a co-operative system between Egypt and Germany, entitled “Biopharmaceutical Studies on Some Cephalosporin Metal Complexes”. He is a professor of pharmaceutics at faculty of pharmacy, King Saud University, Riyadh, KSA, since 2012. He is an author and co-author for many research articles and books. Dr. Auda has holds five patents in the field of pharmaceutics and industrial pharmacy. He also supervised, co-supervised and examined several undergraduate and postgraduate students’ researches.

Mounir M. Salem-Bekhit

Dr. Mounir M. Salem-Bekhit earned his Ph. D. in Pharmaceutical Sciences (Microbiology and Immunology) from Al-Azhar University, Cairo, Egypt in 2005. He spent a one-year postdoctoral fellowship at the NYU School of Medicine, New York, USA, where he was given a Visiting Professor status immediately afterwards. He was appointed a Director of Microbiology Research Center at Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University from 2010-2016. Currently, Salem-Bekhit is a director of Biotechnology lab, College of Pharmacy, King Saud University from 2016-to date. Since 2005, Salem-Bekhit authored and co-authored several peer-reviewed articles and book chapters, and supervised, co-supervised and examined a number of graduate and undergraduate students. He holds four patents in the field of Microbiology. He is a reviewer and editor for many reputable journals. He received several awards including Al-Azhar University Award for Scientific Encouragement for best research publication in 2007 and Rashid Bin Hmeed Award, UAE for best research in Health sciences in 2010.

Ahmad J. Obaidullah

Dr. Ahmad J. Obaidullah is serving as Associate Professor at Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Saudi Arabia. He has published more than 85 research articles in well reputed international impact factor journals. Medicinal Chemistry, Computational chemistry and molecular modeling, Drug design, discovery and development. His research interests focus on area of drug design, discovery and development of new antibacterial, antiviral, anticancer and antihypertensive agents through using many tools such as virtual screening, docking, scoring, Structure-activity relationship.

Maytham T. Qasim

Maytham T. Qasim is having Doctorate degree in Public health. He is serving as Co-Dean at Al-Ayen University. His research interests include immunity, Autoimmunity and Animal Physiology. He has published more than 55 research articles in well reputed journals.

Yacine Benguerba

Yacine Benguerba is a Professor and Researcher in the department of Chemical Engineering at Ferhat Abbas University, Sétif, Algeria. His current research interests include the study of deep eutectic solvents, the adsorption and removal of industrial dyes, heavy metals, and pharmaceuticals, as well as the inhibition of corrosion on metallic surfaces. Additionally, he is engaged in simulating catalytic reactors using advanced reaction models and computational fluid dynamics techniques. Yacine has a significant publication record with nearly 100 research and reviews articles to his credit. He has also presented his research at a variety of international conferences. His research interests encompass a wide range of topics such as molecular modeling, process simulation, catalysis, chemical reactivity, coking, deactivation of catalysts, biocatalysis, fermentation, membrane-based separations, surface phenomena, transfer phenomena, and the design of new materials, including deep eutectic solvents and molecules with therapeutic potential.