Development of a Thermosensitive In-Situ Gel Formulations of Vancomycin Hydrochloride - Design, Preparation, In Vitro and In Vivo Evaluation

Oct 23, 2026

The study develops a thermosensitive in situ gel delivery system for ocular vancomycin, using Poloxamer 407 and Poloxamer 188, to address systemic disease treatment. The formulation is characterized by differential scanning calorimetry, rheology, and drug release studies, followed by rabbit ocular dosing for pharmacokinetics and irritation assessment. The gel remains a flowing liquid at 25°C, becomes semi-solid at 34°C with tear dilution, and prolongs ocular retention. Gel erosion and cumulative drug release show excellent linearity, consistent with zero-order kinetics. Compared with vancomycin eye drops, peak concentration, AUC, and bioavailability increase by 1.44, 1.98, and 1.93 times.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Ocular administration as a systemic delivery route

Materials and Methods

Formulation design and characterization

In vitro evaluation

In vivo pharmacokinetics and irritation tests

Results and Discussion

Thermosensitive behavior and retention

Zero-order release and erosion relationship

Comparative pharmacokinetics versus eye drops

Conclusion

Journal of Pharmaceutical Sciences 111 (2022) 2552−2561 Contents lists available at ScienceDirect Journal of Pharmaceutical Sciences journal [homepage:](homepage: www.jp harmsci. org)[ www.jp harmsci. org](homepage: www.jp harmsci. org) Pharmaceutics, Drug Delivery and Pharmaceutical Technology Development ofa Thermosensitive In-Situ Gel Formulations of Vancomycin Hydrochloride: Design, Preparation, In Vitro and In Vivo Evaluation Luyu Baia,b, Fang Leia, Rui Luoa, Qingsong Feia, Zhiyun Zhenga,c,d,e,*, Ning Hea,c,d,e,*, Shuangying Guia,c,d,e a Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China b College of Biology Engineering, Hefei Technology College, Hefei, 238000, China c Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei, 230012, China d Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, 230012, China e Engineering Technology Research Center of Modern Pharmaceutical Preparation, Anhui Province, Hefei, 230012, China | A R T I C L E I N F O | | A B S T R A C T | | --- | --- | --- | | Article history:
Received 16 November 2021
Revised 13 April 2022
Accepted 13 April 2022
Available online 21 April 2022 | | The purpose of this study was to develop a thermosensitive in situ gel delivery system based on Poloxamer 407 and Poloxamer 188 for ocular administration of vancomycin to treat systemic diseases. The vancomycin thermosensitive in situ gel was characterized using differential scanning calorimetry, rheological and drug release analyses. Additionally, pharmacokinetic studies and irritation tests of the gel were conducted after ocular administration in rabbits. The gel maintained a ﬂowing liquid state under non-physiological conditions (25°C) to facilitate administration, and it transformed into a semi-solid state under physiological conditions (dilution with tears, 34°C), which prolonged its retention time in the eye. The gel erosion and drug release tests showed an excellent linear relationship between the cumulative drug release rate and the cumulative gel erosion rate, indicating a zero-order kinetic process. The pharmacokinetic analyses showed that the peak concentration, area under the curve, and bioavailability of the vancomycin thermosensitive in situ gel were 1.44, 1.98 and 1.93 times greater, respectively, that the values of vancomycin eye drops. Therefore, thermosensitive in situ gel may serve as a drug delivery system that can overcome the limitations of existing formulations of small-molecule peptides.
© 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved. | | Keywords:
Vancomycin hydrochloride
Ocular administration
Thermosensitive in situ gel
Pharmacokinetics | | | Introduction Vancomycin (VCM) is a glycopeptide antibiotic with narrow-spectrum bactericidal effects that has a particular activity against infections caused by methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.1 It is mainly used for systemic, intestinal, and other infections caused by Staphylococcus (including penicillinresistant and neopenicillin-resistant strains) and Clostridium difﬁcile such as endocarditis,2 sepsis,3 osteomyelitis4 and pseudomembranous colitis.5 Endophthalmitis is a serious ophthalmic complication and about 60−80% of cases are caused by Gram-positive bacteria such as S. epidermidis, S. aureus, Streptococcus and Bacillus.6, 7 Many patients eventually develop eyeball atrophy and must undergo * Corresponding authors at: Department of Pharmaceutics, School of Pharmacy, Anhui University of Chinese Medicine. 350 Longzihu Road, Hefei, AnHui, 230012, China. [E-mail addresses:](E-mail addresses: 3348567616@qq.com)[ 3348567616@qq.com](E-mail addresses: 3348567616@qq.com) (Z. Zheng), [hening0826@126.com](hening0826@126.com) (N. He). enucleation because the disease progresses rapidly and treatment i

FAQs

What thermosensitive drug delivery system was developed in the study?

A thermosensitive in situ gel for ocular administration of vancomycin hydrochloride, formulated with Poloxamer 407 and Poloxamer 188.

How was the thermosensitive behavior of the gel evaluated?

Differential scanning calorimetry and rheological assessment were used, alongside state change behavior from a flowing liquid at 25°C to a semi-solid at physiological conditions (34°C with tear dilution).

What pharmacokinetic improvements were observed after ocular administration in rabbits?

Peak concentration, AUC, and bioavailability were reported as 1.44, 1.98, and 1.93 times higher than those of vancomycin eye drops.

Oct 23, 2026

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