Journal of Applied Biopharmaceutics and Pharmacokinetics, 2020, 8, 1-15 1 E-ISSN: 2309-4435/20 © 2020 Scientific Array Formulation of Heterolipid-Based Hollow Nanoparticles Improves the Physicochemical and Gastroprotective Properties of Cimetidine Chukwuebuka Umeyor 1,* , Chioma Chike-Nwankwo 1 , Comfort Madueke 1 , Precious Orji 1 and Anthony Attama 2 1 Nanomedicines and Drug Delivery Research Group, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 422001, Anambra State, Nigeria 2 Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria Abstract: Purpose: The purpose of the present study is to improve the physicochemical and gastroprotective properties of the BCS class III drug, cimetidine using nanostructured lipid carriers (NLC); thus, improving the overall absorption and bioavailability of cimetidine. Methods: Cimetidine-loaded NLCs were formulated by melt-fusion followed by high pressure homogenization (HPH) using rational blends of the solid lipids, Precirol ® ATO5 and beeswax, and the liquid lipid, Kolliphor ® ELP. In vitro physicochemical characterization (particle size, electric charge, polydispersity index, thermal analysis, particle optics, entrapment efficiency) and in vivo gastroprotective evaluations were carried out respectively. Results: Cimetidine-loaded NLCs were stable (-31 to -37 mV), polydispersed (0.1 – 0.4) with particle sizes ranging from 113 – 153 nm. Thermal analysis confirmed that cimetidine was molecularly dispersed in the NLC due to low matrix crystallinity. In vitro release of cimetidine showed sustained release effect and entrapment efficiency (EE %) was concentration-dependent in the range of 85 – 96 %. There was improved gastric ulcer inhibition by the cimetidine-loaded nanoparticles. Conclusion: The improved physicochemical and gastroprotective profiles obtained from the study suggest that NLC is a very promising delivery system for cimetidine. Keywords: Cimetidine, Precirol ® ATO5, Beeswax, Gastroprotective, Nanostructured lipid carrier. INTRODUCTION Peptic ulcer disease (PUD) including gastric and duodenal ulcers, is an important GI disorder which occurs as a deep and severe injury or lesion in the GIT. Depending on the depth of the lesion, PUD might erode the muscularis mucosae due to its aggressive negative effect on the mucosal defenses. It is often characterized by burning sensation in the epigastrium, belching, nausea, vomiting, oedema, bleeding, scarring, gastric perforation, haemorrhage, and gastric outlet obstruction [1-3]. The exact aetiology of PUD is not clear, but it is reportedly caused by factors like hyperacidity in the gastric mucosa, imbalance between the aggressive acid-pepsin secretions and impaired mucosal resistance, infection by Helicobacter pylori, and misuse of non-steroidal anti-inflammatory drugs (NSAIDs). It has also been reported that hereditary conditions could lead to ulcers but the mechanism is Address correspondence to this author at the Nanomedicines and Drug Delivery Research Group, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka 422001, Anambra State, Nigeria; Tel: +234-8063299850; E-mail: ec.umeyor@unizik.edu.ng not yet clear [4, 5]. Cimetidine (N-cyano-N-methyl-N- [2([(5-methyl-1H-imidazol-4-yl) methyl] thio) ethyl] guanidine is the first drug developed for the clinical treatment of PUD, dyspepsia and gastroesophageal reflux disease (GERD) by GlaxoSmithKline and marketed as Tagamet ® [6]. According to the biopharmaceutical classification system (BCS), cimetidine is a class III drug, and drugs in this class account for about 25 % of drugs used in the US, and about 40 % of drugs listed in the World health Organization (WHO) List of Essential Medicines [7, 8]. Generally, drugs in this class have high solubility and low permeability. However, cimetidine is sparingly soluble (11.4 mg/ml at 37 °C), undergoes incomplete absorption following oral administration with low intestinal permeation. Consequently, the incomplete solubilization and absorption of cimetidine, especially in PUD, lead to unpredictable bioavailability and irreproducible clinical response or outright therapeutic failure [9]. Recently, the development and introduction of lipid nanoparticles as an acceptable alternative delivery system to tablets and capsules for solving incomplete