Chitosan Spray-Dried Microparticles for Controlled Delivery of Venlafaxine Hydrochloride

Abstract

Venlafaxine controlled drug delivery systems using different matrixes have been tested to reduce undesirable side effects in the treatment of depression. The legal status of chitosan (Cs) in Pharmacy has dramatically improved after its acceptance as excipient in several Pharmacopeias and, therefore, there is great interest in pharmaceutical formulations based on this polymer. In this paper, chitosan microcapsules cross-linked with sodium tripolyphosphate (TPP) for oral delivery of venlafaxine were formulated using the spray drying technique. The effect of chitosan physico-chemical properties, TPP concentration and TPP/Cs ratio on drug release was evaluated. The microcapsules were characterized in terms of size, zeta potential and morphology. The physical state of the drug was determined by X-ray diffraction (XRD) and the drug release from the microcapsules was studied in simulated gastric and intestinal fluids. The release pattern fitted well to the Peppas-Koersmeyer model with n exponents indicating anomalous transport.

Investigations of the Influences of Processing Conditions on the Properties of Spray Dried Chitosan-Tripolyphosphate Particles loaded with Theophylline

“…Therefore, although a tunable drug release could be obtained by altering cross-linking ratios of the chitosan-TPP system, the amount of TPP added must not be too high to avoid the undesired agglomeration phenomena due to the neutralized zeta potential values. As reported, zeta potential values of spray-dried chitosan particle were around +26 mV 41,49 , with the addition of TPP at 0.1% (w/v) dropping the values to +21 mV 41 , from which the TPP content investigated in our study (Table 3, with the weight to volume percentage of TPP in chitosan precursor solution, was ranged from 0.006 to 0.04% (w/v) < 0.1% (w/v)) should not be a concern regarding the TPP induced zeta potential drops.…”

“…In this study, TH was selected as a drug target model because of its widespread application in anti-inflammatory treatments with remarkable effects when the drug was delivered using polymeric carrier 20,23,39 . The release behavior of the TH from spray-dried chitosan-TPP particles was discussed by performing the dissolution test in phosphate buffer solution at a fixed pH of 7.4 to mimic the physiological values of intravenous (IV) administration 40 or simulated intestinal fluid 41 at constant precursor solution concentrations of TH and chitosan, 0.02 w/v% and 0.1 w/v%, respectively. TH releasing behaviors in buffers at a gastric fluid (pH 1.2) might be changed but not discussed here 42 .…”

“…For example, particle sizes of spray-dried chitosan particles had been reported to be determined not only by the spray drying process parameters but also by the precursor concentration of feed solutions 7 . Furthermore, chitosan particles made by spray drying without cross-linker addition was known to be easily aggregated due to its swelling and dissolution properties 7,14 . The addition of a crosslinking agent in a precursor solution is then another required parameter that needs to be controlled for a better drug delivery design.…”

“…Since commonly used cross-linking agents such as glutaraldehyde are toxic 15 , it is not allowed in pharmaceutical applications. Tripolyphosphate (TPP) anions were then used as a cross-linking agent of chitosan in this study due to its low toxic nature 7,14,16 . TPP can interact with cationic chitosan through electrostatic forces 17 , with the free amino groups in chitosan carrying positive charges for crosslinking reaction with negatively charged anions from TPP.…”

Chitosan Microspheres as Carriers for pH‐Indicating Species in Corrosion Sensing

“…The assumption that a total release is obtained when performing studies in alkaline conditions is based on the solubility and swelling of the chitosan microspheres . Although chitosan itself is only soluble at low pH, chitosan microspheres are made of chitosan acid salts (more specifically acetate salts since chitosan is dissolved in acetic acid, before spray drying) and these are known to be water soluble, which may contribute to a higher swelling and dissolution, allowing the complete release of the pH indicator dyes present in the particles.…”