title: Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept.
abstract: BACKGROUND
  The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability.
  
  
  OBJECTIVE
  The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation.
  
  
  METHODS
  The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug.
  
  
  CONCLUSIONS
  Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed Tmax, improved Cmax and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption.
  
  
  CONCLUSIONS
  According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.
authors.affiliation: a Department of Pharmaceutical Sciences , Saurashtra University , Rajkot , Gujarat , India ;
authors.forename: Nirav
authors.initials: N
authors.lastname: Patel
authors.affiliation: b Anand Pharmacy College , Anand , Gujarat , India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Thakkar
authors.affiliation: b Anand Pharmacy College , Anand , Gujarat , India.
authors.forename: Viral
authors.initials: V
authors.lastname: Metalia
authors.affiliation: b Anand Pharmacy College , Anand , Gujarat , India.
authors.forename: Lalji
authors.initials: L
authors.lastname: Baldaniya
authors.affiliation: b Anand Pharmacy College , Anand , Gujarat , India.
authors.forename: Tejal
authors.initials: T
authors.lastname: Gandhi
authors.affiliation: b Anand Pharmacy College , Anand , Gujarat , India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Gohel
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000737:chemistry; D015817:Eye Infections / Q000188:drug therapy*; D005260:Female; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D065347:Hypromellose Derivatives / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D013696:Temperature; D014031:Tobramycin / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D009883:Ophthalmic Solutions; D020442:Poloxamer; C004180:dexamethasone 21-phosphate; D065347:Hypromellose Derivatives; D003907:Dexamethasone; D014031:Tobramycin
keywords: Central composite design; Poloxamer 407; dexamethasone sodium phosphate; eye irritation study; hydroxy propyl methyl cellulose (HPMC) K4M; pharmacokinetic study; tobramycin sulfate