Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable prop... more Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable proper formulation screening before nanosizing can be performed on a large scale. Ideally, the information generated at small scale is predictive for large scale production. Objective: This study was aimed to investigate the scalability when producing nanosuspensions starting from a 10 g scale of nanosuspension using low energy wet ball milling up to production scales of 120 g nanosuspension and 2 kg nanosuspension by using a standard high energy wet ball milling operated in batch mode or recirculation mode, respectively. Methods: Two different active pharmaceutical ingredients, i.e. curcumin and hesperetin, have been used in this study. The investigated factors include the milling time, milling speed, and the type of mill. Results: Comparable particle sizes of about 151 nm to 190 nm were obtained for both active pharmaceutical ingredients at the same milling time and milling speed when the ...
The role of a surface modifier is important in the formation of stable nanosuspensions. In this s... more The role of a surface modifier is important in the formation of stable nanosuspensions. In this study, a simple and systematic screening method for selecting optimum surface modifiers was performed by utilizing a low-energy wet ball milling method. Nine surface modifiers from different classes with different stabilization mechanisms were applied on six different models of active pharmaceutical ingredients (API). Particle size analysis showed that at concentration five times higher than the critical micelle concentration, SDS and sodium cholate (anionic surfactant) showed the highest percent success to produce stable nanosuspensions with particle size smaller than 250 nm. Similar findings were also shown by poloxamer 188 (nonionic surfactant) and hydroxypropylmethylcellulose E5 (polymeric stabilizer) at concentration 1% (w/v) and 0.8% (w/v), respectively. In addition, combinations of anionic surfactant and nonionic surfactant as well as combinations of anionic surfactant and polymeric stabilizer showed high percent success in the formation of stable nanosuspensions. In general, no correlation can be found between the physicochemical characteristics of the model API (molecular weight, melting point, log P, pKa, and crystallinity) with its feasibility to be nanosized. The concentration and the principle of stabilization of surface modifier determine the formation of stable nanosuspensions.
Profiles of Drug Substances, Excipients and Related Methodology, 2011
Glimepiride, which belongs to the sulfonylurea group, has been widely analyzed for its physical c... more Glimepiride, which belongs to the sulfonylurea group, has been widely analyzed for its physical chemical properties including its crystallinity. Moreover, methods to quantify glimepiride and its impurities, either in pharmaceutical dosage form or in biological sample, have also been extensively developed and reported. This chapter extracts all information needed to give more perspective regarding to this substance.
A novel flow through (FT) diffusion cell for assessing the permeability of compounds across the b... more A novel flow through (FT) diffusion cell for assessing the permeability of compounds across the buccal mucosa was designed. Porcine buccal mucosa was mounted between two chambers with flow through capacity in both the donor and receptor chambers. The permeability of caffeine (CAF), triamcinolone acetonide (TAC), and estradiol (E(2)) was determined over 4 h and flux values were compared to those obtained using a modified Ussing chamber (MUC). No significant differences in the flux of each probe compound were observed using either the MUC or the novel FT cell. The design of the FT cell allowed for monitoring appearance of receptor solution within the donor chamber during the initial equilibration period, allowing for visual inspection of tissue integrity. These permeability studies demonstrate that this FT cell is a suitable alternative model for assessing drug permeability across the buccal mucosa, without the limitations associated with the static MUC. This novel model was then utilized to determine whether salmeterol xinafoate (SX) could permeate the buccal mucosa at concentrations expected in the oral cavity following inhalation. Concentration-dependent studies demonstrated that SX permeates the buccal mucosa via passive diffusion and that oral mucosal absorption may contribute significantly to the overall systemic exposure of inhaled SX.
Journal of Liquid Chromatography & Related Technologies, 2004
... From the Analytical Abstracts Database. For the latest techniques and applications in the ana... more ... From the Analytical Abstracts Database. For the latest techniques and applications in the analytical sciences. RSC Journals. HPLC determination of cilostazol in tablets and its validation. AD Lestari, T. Palupi, B. Oktarina, M. Yuwono and G. Indrayanto J. Liq. Chromatogr. Relat. ...
Objective: The objective of this research was to enhance the dissolution characteristic of diterp... more Objective: The objective of this research was to enhance the dissolution characteristic of diterpene lactone fraction of Andrographis paniculata Nees (DTLF) containing 75.9% andrographolide. The effect of carboxymethyl chitosan concentration on physical characteristics, entrapment efficiency and in vitro release of diterpene lactone fraction of Andrographis paniculata Nees (DTLF) particulate system were investigated. Methods : Diterpene lactone fraction of Andrographis paniculata Nees (DTLF) particulate system with different amount of carboxymethyl chitosan (CMChi) were prepared by ionic gelation followed by spray drying methods with CaCl 2 as cross linker. The particles were evaluated in terms of physical state, drug entrapment efficiency and in vitro release rate. R e s u l t s : T h e r e s u l t s h o w e d t h a t D T L F i s a l r e a d y e n t r a p p e d i n t h e s y s t e m h e n c e t h e crystallinity reduced. The entrapment efficiency increases with increasing the amount of carboxymethyl chitosan, between 84% up to 90%. The release rate of the particles in 0.5% SLS media were 1.5 times higher than DTL substance, but not significantly different as the polymer amount increased. Conclusion : Entrapment of DTL in CMChi particulates system could reduce the crystallinity. Hence DTL – CMChi particles were able to enhance release rate of DTL up to 1.5 times.
Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable prop... more Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable proper formulation screening before nanosizing can be performed on a large scale. Ideally, the information generated at small scale is predictive for large scale production. Objective: This study was aimed to investigate the scalability when producing nanosuspensions starting from a 10 g scale of nanosuspension using low energy wet ball milling up to production scales of 120 g nanosuspension and 2 kg nanosuspension by using a standard high energy wet ball milling operated in batch mode or recirculation mode, respectively. Methods: Two different active pharmaceutical ingredients, i.e. curcumin and hesperetin, have been used in this study. The investigated factors include the milling time, milling speed, and the type of mill. Results: Comparable particle sizes of about 151 nm to 190 nm were obtained for both active pharmaceutical ingredients at the same milling time and milling speed when the ...
The role of a surface modifier is important in the formation of stable nanosuspensions. In this s... more The role of a surface modifier is important in the formation of stable nanosuspensions. In this study, a simple and systematic screening method for selecting optimum surface modifiers was performed by utilizing a low-energy wet ball milling method. Nine surface modifiers from different classes with different stabilization mechanisms were applied on six different models of active pharmaceutical ingredients (API). Particle size analysis showed that at concentration five times higher than the critical micelle concentration, SDS and sodium cholate (anionic surfactant) showed the highest percent success to produce stable nanosuspensions with particle size smaller than 250 nm. Similar findings were also shown by poloxamer 188 (nonionic surfactant) and hydroxypropylmethylcellulose E5 (polymeric stabilizer) at concentration 1% (w/v) and 0.8% (w/v), respectively. In addition, combinations of anionic surfactant and nonionic surfactant as well as combinations of anionic surfactant and polymeric stabilizer showed high percent success in the formation of stable nanosuspensions. In general, no correlation can be found between the physicochemical characteristics of the model API (molecular weight, melting point, log P, pKa, and crystallinity) with its feasibility to be nanosized. The concentration and the principle of stabilization of surface modifier determine the formation of stable nanosuspensions.
Profiles of Drug Substances, Excipients and Related Methodology, 2011
Glimepiride, which belongs to the sulfonylurea group, has been widely analyzed for its physical c... more Glimepiride, which belongs to the sulfonylurea group, has been widely analyzed for its physical chemical properties including its crystallinity. Moreover, methods to quantify glimepiride and its impurities, either in pharmaceutical dosage form or in biological sample, have also been extensively developed and reported. This chapter extracts all information needed to give more perspective regarding to this substance.
A novel flow through (FT) diffusion cell for assessing the permeability of compounds across the b... more A novel flow through (FT) diffusion cell for assessing the permeability of compounds across the buccal mucosa was designed. Porcine buccal mucosa was mounted between two chambers with flow through capacity in both the donor and receptor chambers. The permeability of caffeine (CAF), triamcinolone acetonide (TAC), and estradiol (E(2)) was determined over 4 h and flux values were compared to those obtained using a modified Ussing chamber (MUC). No significant differences in the flux of each probe compound were observed using either the MUC or the novel FT cell. The design of the FT cell allowed for monitoring appearance of receptor solution within the donor chamber during the initial equilibration period, allowing for visual inspection of tissue integrity. These permeability studies demonstrate that this FT cell is a suitable alternative model for assessing drug permeability across the buccal mucosa, without the limitations associated with the static MUC. This novel model was then utilized to determine whether salmeterol xinafoate (SX) could permeate the buccal mucosa at concentrations expected in the oral cavity following inhalation. Concentration-dependent studies demonstrated that SX permeates the buccal mucosa via passive diffusion and that oral mucosal absorption may contribute significantly to the overall systemic exposure of inhaled SX.
Journal of Liquid Chromatography & Related Technologies, 2004
... From the Analytical Abstracts Database. For the latest techniques and applications in the ana... more ... From the Analytical Abstracts Database. For the latest techniques and applications in the analytical sciences. RSC Journals. HPLC determination of cilostazol in tablets and its validation. AD Lestari, T. Palupi, B. Oktarina, M. Yuwono and G. Indrayanto J. Liq. Chromatogr. Relat. ...
Objective: The objective of this research was to enhance the dissolution characteristic of diterp... more Objective: The objective of this research was to enhance the dissolution characteristic of diterpene lactone fraction of Andrographis paniculata Nees (DTLF) containing 75.9% andrographolide. The effect of carboxymethyl chitosan concentration on physical characteristics, entrapment efficiency and in vitro release of diterpene lactone fraction of Andrographis paniculata Nees (DTLF) particulate system were investigated. Methods : Diterpene lactone fraction of Andrographis paniculata Nees (DTLF) particulate system with different amount of carboxymethyl chitosan (CMChi) were prepared by ionic gelation followed by spray drying methods with CaCl 2 as cross linker. The particles were evaluated in terms of physical state, drug entrapment efficiency and in vitro release rate. R e s u l t s : T h e r e s u l t s h o w e d t h a t D T L F i s a l r e a d y e n t r a p p e d i n t h e s y s t e m h e n c e t h e crystallinity reduced. The entrapment efficiency increases with increasing the amount of carboxymethyl chitosan, between 84% up to 90%. The release rate of the particles in 0.5% SLS media were 1.5 times higher than DTL substance, but not significantly different as the polymer amount increased. Conclusion : Entrapment of DTL in CMChi particulates system could reduce the crystallinity. Hence DTL – CMChi particles were able to enhance release rate of DTL up to 1.5 times.
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Papers by Maria Ardhani Dwi Lestari