Pharmaceutical production :

Preparation  and evaluation  of  a  sustained-release suspension  containing  theophylline  microcapsules Jaber  Emami1,  Jaleh  Varshosaz1,  Mohammadreza  Amirsadri1  and Fatemeh  Ahmadi2,3* 1Department of  Pharmaceutics, Faculty  of  Pharmacy  and  Pharmaceutical  Sciences,   Isfahan  University  of  Medical  Sciences, Isfahan, Iran. 2Department of  Pharmaceutics, Faculty  of  Pharmacy,  Shiraz  University  of  Medical  Sciences,  Shiraz, Iran. 3Cardiovascular Research  Centre,  Fasa University  of  Medical  Sciences, Fasa,  Iran. Accepted  9  July,  2012 A  great  effort  has  been  devoted  to  the  preparation  of  sustained-release  formulations  of  theophylline  to prevent  large  fluctuations  of  serum  concentration  and  increasing  the  therapeutic  efficacy  followed  by patient  compliance.  In  the  present  study,  microcapsules  of  theophylline  with  ethyl  cellulose  (EC)  were prepared  by  emulsion-solvent  evaporation  method  in  different  polymer  to  drug  ratios.  Size, morphology,  drug  loading  and  release  behavior  of  microcapsules  were  also  studied.  Microcapsules were  then  formulated  into  suspensions  to  provide  an  oral  liquid  dosage  form  for  drug  and  resulting suspensions  were  examined  for  stability  and  release  characteristics  in  various  storage  times.  Results showed  that  microcapsules  prepared  in  drug  to  polymer  ratio  1:1.4  by  emulsifying  polymer  solution  in liquid  paraffin  presented  the  sustained-release  properties  which  met  the  United  States  Pharmacopeia (USP)  (2007)  requirements  (t50%  and  t80%  of  these  microparticles  were  150  and  360  min,  respectively). The  suspensions  prepared  by  these  microcapsules  were  also  stable  in  the  study  period  and  their release  profiles  were  consistent  to  the  original  microcapsules.  The  results  allow  for  the  conclusion  that the  formulated  suspension  can  be  used  as  a  sustained-release  formulation  for  theophylline  in  treatment of  obstructive pulmonary  disorders.         Key  words:  Theophylline,  microencapsulation,  suspension,  sustained-release,  ethyl  cellulose. INTRODUCTION Theophylline  is  a  methylxanthine  alkaloid  which  is  used as  bronchodilator  in  treatment  of  chronic  obstructive pulmonary  disorders  especially  asthma.  Although,  it  is used  for  about  70  years,  the  complications  associated with  its  use  are  still  unsolved  (Obeidat  et  al.,  2009;  Soni et  al.,  2010).  Theophylline  is  a  narrow  therapeutic  index drug  with  a  short  half-life.  Conventional  dosage  forms  of theophylline  should  be  administered  3  to  4  times  a  day  to provide  effective  concentration  and  to  avoid  large fluctuations  in  blood  concentration.  This  leads  to  poor patient  compliance  and  enhanced  risk  of  gastrointestinal (GI)  and  cardiovascular  adverse  effects.  Sustained- release     formulations      would       provide        steady       blood *Corresponding  author.  E-mail:  ahmadi_f@sums.ac.ir.  Tel:  +98 (711)  2424128  (Ext  272).  Fax:  +98  (711) 2424126. concentrations  with  minimum  fluctuation  and  results  in higher  therapeutic  efficacy  and  lower  risk  of  toxicity  (Roy et  al., 2007; Zhang  et  al., 2008). Among  sustained-release  drug  delivery  systems, microcapsules  have  received  much  attention  because  of uniform  distribution  in  GI  tract  which  leads  to  uniform absorption  and  decreasing  risk  of  local  effects  on  GI  tract. Another  advantage  of  microparticulate  systems  is  their feasibility  to  be  incorporated  into  liquid  dosage  forms such  as  suspensions.  In  addition  to  sustain  the  drug release,  microencapsulation  of  theophylline  can  decrease its  irritating  effect  on  GI  mucosa  and  mask  drug  taste (Lavasanifar  et  al.,  1997).  Due  to  ease  of  swallowing  and flexibility  in  dosage  adjustment,  liquid  dosage  forms  are preferred  especially  in  pediatric  and  geriatric  patients (Bodmeier  et  al.,  1991;  Cuña  et  al.,  2000).  Different techniques  of  microencapsulation  have  been  developed for       controlled      delivery     of     different    drugs     including