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KMID : 1146920180480030279
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Journal of Pharmaceutical Investigation
2018 Volume.48 No. 3 p.279 ~ p.293
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Reverse engineering and formulation by QBD of olopatadine hydrochloride ophthalmic solution
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Ahmed Zahid Zaheer
Khan Furquan Nazimuddin
Shaikh Darakhshan Afreen
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Abstract
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Reverse engineering of innovator product’s formulation is a cost-effective strategy for accelerating generic product development. The total market share for olopatadine hydrochloride (OLH) ophthalmic solution used as an antihistamine in US is nearly $230 million dollars. By using ‘Differential solubility technique’ and 32 factorial designs for separation of components, nine different batches were prepared. The separated quantities of OLH and excipients i.e. benzalkonium chloride (BKC), sodium chloride (NaCl) and sodium phosphate dibasic (Na2HPO4) were 0.111, 0.01, 0.65 and 0.5 g respectively. Statistical analysis by ANOVA resulted significant model having P values <0.0001 for BKC and 0.0001 for OLH. X-ray diffraction study revealed that separated OLH was found to be polymorphic form A with characteristic 2θ values of 15.44°, 17.55°, 18.20°, 18.971°, 20.58°, 20.68°, 23.89°, 25.30°, 28.25°. The differential scanning calorimetry of OLH gave an endothermic peak at approximately 255?°C. The refractive index of separated BKC was 1.4. Based upon the reverse engineering data generic form of OLH was prepared with pH of 7.1?±?0.3; osmolarity of 302?±?1.5 mOsmol/l, assay of 99?±?2% and viscosity of 0.9715?±?0.12 pas. The prepared generic formulation of OLH is equivalent and stable with marketed formulation of OLH.
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KEYWORD
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Reverse engineering (RE), Quality by design (QBD), Olopatadine hydrochloride (OLH), Antihistamine, Design of experiment (DOE)
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