Abstract: The objective of this research is to study the application of Pregelatinized Cassava Starch Succinate (PCSS), a physically and chemically modified starch and the combinations with Carbopol 974P and hydroxypropylmethyl cellulose (HPMC) for preparing mucoadhesive microspheres by the spray-drying technique. The obtained-microspheres were characterized, including: morphology, particle size distribution, entrapment efficiency and mucoadhesive strength on the stomach and intestinal of rats. In addition, the in vitro drug release from the microspheres was performed in pH 1.2 and 7.2. The results showed that the produced microspheres of PCSS and its combination with HPMC and Carbopol 974P were irregular shape with a rough surface morphology and have particles sizes range of 2.5-28 μm. Propanolol hydrochloride (PH) was incorporated into the microspheres with an efficiency of range between 84-100%. On gastric mucosa, the microspheres of PCSS, HPMC and PCSS-HPMC were more mucoadhesive than the microspheres of Carbopol 974P and PCSS-Carbopol 974P. On the other hand, all kinds of the microspheres show good mucoadhesive properties on intestinal mucosa. Furthermore, the drug release from the microspheres produced pH-dependent extended-release in pH 1.2 HCl and pH 7.2 phosphate medium. During 8 h in vitro release study, the release of propanolol hydrochloride from the microspheres of PCSS-HPMC and PCSS-Carbopol 974P in pH 7.2 was slower than that in pH 1.2. The findings obtained revealed that PCSS microspheres have good mucoadhesive property on both of gastric and intestinal mucosa. Moreover, the addition of HPMC and Carbopol 974P to PCSS hydrophilic matrix significantly extended the drug release.