Optimization of Formulations of Metoprolol Succinate Tablets Containing Ofada Rice Starch Acetate as Tablet Matrix for Sustained Release Using Response Surface Methodology

Background: Release-retarding polymers in matrix tablets play a vital role in controlling drug release from tablets.Objectives: To prepare metoprolol succinate tablets by direct compression using Ofada rice (Oryza glaberrima Steud) starch acetate, degree of substitution (DS) 2.22, as a matrix for sustained release.Materials and methods: The central composite design and response surface methodology were applied to evaluate the interactive effects of three variables: percent content of starch acetate (X1), compression pressure (X2) and compression time (X3), on tablet crushing strength, friability and dissolution time (t80).Results: Crushing strength was 90.0 to 140.50 N; Friability 0.05 to 0.90 % and t80 5.75 to 11.50 h. X1 and X2 had significant effects on crushing strength and dissolution time (p < 0.0001). The interactions between X1 and X2 and those between X1 and X3 were significant on crushing strength and dissolution time, and on friability respectively (p < 0.0001). The correlation coefficients indicated that the regression model represented the experimental data well (R2 = 0.9971 and R2 (Adj) = 0.9944 for crushing strength; R2 = 0.9976 and R2 (Adj) = 0.9954 for friability; R2 = 0.9979 and R2 (Adj) = 0.9961 for t80). Optimized conditions for formulation of metoprolol succinate tablets were 60 %w/w Ofada starch acetate; 150 MNm-2 compression pressure and 60 s compression time.Conclusion: Optimized formulations of metoprolol tablets containing Ofada starch acetate with good mechanical strength and prolonged dissolution can be obtained when process conditions are adjusted within the reported values.Keywords: Central composite design, Metoprolol succinate tablets, Ofada rice starch acetate, Response surface methodolog

Evaluation of Three Tropical Starches as Superdisintegrants in Fast Dissolving Tablets of Domperidone Using a Taguchi-Based Design of Experiments

A Taguchi-based design of experiments was employed to optimize fast-dissolving tablet formulations of domperidone using three starches from banana (Musa acuminata), cassava (Manihot esculenta) and Chinese yam (Dioscorea rotundata). The starches were modified by carboxymethylation (degree of substitution 0.32±0.02) and used as superdisintegrants (2–8%w/w), in comparison to sodium starch glycolate (SSG). Effects of two variables (superdisintegrant type and superdisintegrant concentration) at four levels on crushing strength-friability ratio (CSFR), disintegration time (DT) and dissolution time to 80% drug release (t80) were analyzed. Domperidone tablets containing carboxymethylated starches had higher CSFR values (p<0.05) than SSG while DT and t80 decreased with concentration. Taguchi’s delta values and analysis of variance showed that superdisintegrant type had greater influence on CSFR and t80 while superdisintegrant concentration had greater influence on DT. Optimum fastdissolving domperidone tablets were obtained using 2% w/w Chinese yam starch (CSFR= 251.25±16.32) and 8% w/w SSG (DT = 0.42±0.03 min; t80 = 0.50±0.02 min)

Impact of degree of substitution of acetylated Ofada rice starch polymer on the release properties of nimesulide microspheres

Nimesulide microspheres were prepared by the quasi-emulsion solvent diffusion method, using acetylated starches of the indigenous Ofada rice (Oryza glaberrima Steud) with degrees of substitution (DS) 1.42 and 2.62. Full 23 factorial experimental design was performed using DS (X1), drug: polymer ratio (X2) and polymer concentration (X3) as independent factors; size, entrapment, swelling and time taken for 80% drug release (t80) were the dependent variables.Contour plots were generated and data from in vitro release studies were fitted to various kinetic models. Nimesulide microspheres were near -spherical, with size 50.91±16.22 to 74.24±24.73 µm for microspheres containing starch DS 1.42 and 21.05±4.25 to 46.10±3.85 µm for starch DS 2.62. Drug entrapment was 56.75±0.45 to 98.28±2.30 %. DS had the most influence on size, swelling and dissolution time (p = 0.01) and this was confirmed from the contour plots. The interaction between factors DS and drug: polymer ratio (X1X2) had the highest influence on microsphere properties (p = 0.04). Drug release fitted into first order, Higuchi and Korsmeyer models.  Acetylated starch of Ofada rice DS 2.62 was found more suitable for the formulation of microspheres with reduced size, and swelling, higher entrapment and prolonged drug release.

Characterization and evaluation of acid-modified starch of Dioscorea oppositifolia (Chinese yam) as a binder in chloroquine phosphate tablets

Chinese yam (Dioscorea oppositifolia) starch modified by acid hydrolysis was characterized and compared with native starch as a binder in chloroquine phosphate tablet formulations. The physicochemical and compressional properties (using density measurements and the Heckel and Kawakita equations) of modified Chinese yam starch were determined, and its quantitative effects as a binder on the mechanical and release properties of chloroquine phosphate were analyzed using a 2³ full factorial design. The nature (X1), concentration of starch (X2) and packing fraction (X3) were taken as independent variables and the crushing strength-friability ratio (CSFR), disintegration time (DT) and dissolution time (t80) as dependent variables. Acid-modified Chinese yam starch showed a marked reduction (pAmido de inhame chinês (Dioscorea oppositifolia), modificado por meio de hidrólise ácida, foi caracterizado e avaliado como aglutinante em formulações de comprimidos de fosfato de cloroquina, em comparação com o amido nativo. Determinaram-se as propriedades físico-químicas e de compressão (utilizando medidas de densidade e as equações de Heckel e Kawakita). Os efeitos quantitativos do amido modificado como ligante sobre as propriedades mecânicas e de liberação de fosfato de cloroquina foram analisados por meio de um planejamento fatorial completo 2³. Tomaram-se a natureza (X1), a concentração de amido (X2) e a fração de empacotamento (X3) como variáveis independentes e relação força de compressão-friabilidade (RFCE), tempo de desintegração (DT) e tempo de dissolução (t80), como variáveis dependentes. O amido de inhame chinês modificado mostrou redução marcante (

Evaluation of starches obtained from four Dioscorea species as binding agent in chloroquine phosphate tablet formulations

AbstractStarches obtained from four Dioscorea species namely Dioscorea dumetorum (Bitter), Dioscorea oppositifolia (Chinese), Dioscorea alata (Water), and Dioscorea rotundata (White) have been evaluated as binding agents in chloroquine phosphate tablet formulations in comparison with official corn starch. The compressional properties of the formulations were analyzed using density measurements and the Heckel and Kawakita equations. The mechanical properties of the tablets were assessed using tensile strength, brittle fracture index (BFI), and friability tests while the drug release properties of the tablets were assessed using disintegration and dissolution times. The results indicate that the four starches vary considerably in their physicochemical properties. The ranking for the tensile strength and the disintegration and dissolution times for the formulations was Chinese>Bitter>Corn>White>Water while the ranking was reversed for BFI and friability. The results suggest that Water, White, and Corn could be useful when faster disintegration time of tablets is desired while Chinese and Bitter could be more useful when bond strength is of concern and in minimizing the problems of lamination and capping in tablet formulation

Flow, compaction and tabletting properties of co-processed excipients of pregelatinized Ofada rice starch and HPMC

The growing popularity of direct-compression process necessitates an ideal filler–binder that can substitute two or more excipients. Pregelatinization of starches significantly improve swelling and flow properties but produce tablets with low mechanical strength. When used as binder in many tablet formulations, hydroxyl propyl methyl cellulose (HPMC) imparts mechanical strength but because of its poor flow during high speed tablet manufacturing, granulation of HPMC-based formulations is required. Directly-compressible co-processed excipients were developed utilizing pregelatinized starch of the indigenous Ofada rice starch (Oryza glaberrima Steud Family Poaceae) and HPMC. Co-processed excipients of various combinations of pregelatinized Ofada rice starch and HPMC were prepared using co-fusion method (97.5:2.5; 95:5; 92.5:7.5; 90:10;85:15; 80:20). The flow and compaction properties of the co-processed excipients as well as individual excipients were evaluated using densities, Hausner’s ratio, Carr’s index, angle of repose, angle of internal friction, Kawakita model, consolidation index and rate. Aceclofenac tablets were formulated with starch, HPMC and selected co-processed excipients as filler-binders using direct compression. Pregelatinization produced starch with larger granules and improved flow. FTIR spectra of the co-processed excipients confirmed absence of chemical interaction. Angle of repose, Hausner’s ratio, Carr’s index, angle of internal friction indicated flow properties increased with starch content of the co-processed excipients. Kawakita plots, consolidation index and consolidation rate revealed cohesiveness while compressibility and rate of packing were enhanced. Aceclofenac tablets containing co-processed excipients had crushing strength ≥ 66.03 ± 1.58 MNm-2; friability ≤ 1 %; disintegration time ≤ 10.75 ±3.10 and dissolution time (t80) ≤ 30.00 ± 3.07. The optimized formulation contained Ofada starch: HPMC 95:5. The co-processed excipients of pregelatinized Ofada rice starch and HPMC could serve as suitable, cheaper alternatives to other synthetic excipients for direct compression of tablets

Formulation optimization of floating microbeads containing modified Chinese yam starch using factorial design

Controlled release floating metformin hydrochloride microbeads have been prepared and optimized using a blend of varying concentrations of freeze-dried pregelatinized Chinese yam (Dioscorea oppositifolia) starch and sodium alginate. Floating microbeads were prepared by the ionotropic gelation method using 10% w/v calcium chloride as the cross-linking agent and sodium bicarbonate as the gas releasing agent. A full 32 factorial design was used to investigate the influence of two variables: concentrations of starch (X1) and sodium bicarbonate (X2) on the swelling, floating lag time and amount of drug released after 1 hour (Q1) and 10 hours (Q10). Potential variables such as the concentrations of drug and total polymer were kept constant. The results showed that the properties of the floating microbeads were significantly (

Impact of degree of substitution of acetylated Ofada rice starch polymer on the release properties of nimesulide microspheres

Nimesulide microspheres were prepared by the quasi-emulsion solvent diffusion method, using acetylated starches of the indigenous Ofada rice (Oryza glaberrima Steud) with degrees of substitution (DS) 1.42 and 2.62. A full 23 factorial experimental design was performed using DS (X1), drug:polymer ratio (X2) and polymer concentration (X3) as independent factors; size, entrapment, swelling and time taken for 80% drug release (t80) were the dependent variables. Contour plots were generated and data from the in vitro release studies were fitted to various kinetic models. Nimesulide microspheres were near-spherical, sizes varying from 50.91±16.22 to 74.24±24.73 μm for microspheres containing starch DS 1.42 and from 21.05±4.25 to 46.10±3.85 μm for starch DS 2.62. Drug entrapment was 56.75±0.45 to 98.28±2.30%. DS had the greatest effect on the size, swelling and dissolution time (p = 0.01) which was confirmed by the contour plots. The interaction between factors DS and drug:polymer ratio (X1X2) had the greatest effect on the microsphere properties (p = 0.04). Drug release was fitted into the First Order, Higuchi and Korsmeyer models. Acetylated starch of Ofada rice DS 2.62 was found more suitable for the formulation of microspheres because of reduced size and swelling, higher entrapment and prolonged drug release

Development of Theophylline Microbeads Using PregelatinizedBreadfruit Starch (Artocarpus altilis) as a Novel Co-polymer for Controlled Release

Purpose: The aim of this study was to prepare formulations of theophylline microbeads usingpregelatinized breadfruit starch (Artocarpus altilis, family Moraceae) in combination withsodium alginate and chitosan at various polymer: drug ratios. Microbead formulations forcontrolled delivery of theophylline would be better alternatives to conventional dosage formsfor optimized drug therapy.Methods: The native and pregelatinized starches were characterized for morphology (scanningelectron microscope), crystallinity (Fourier transform intra-red spectroscopy, FTIR and X-raydiffractometer, XRD), thermal flow (differential scanning colorimeter), density and flowproperties. Theophylline microbeads were prepared by ionic gelation and characterized usingsize, swelling index, entrapment efficiency and time required for 15% and 50% drug release (t15and t50 respectively).Results: FTIR and XRD spectra revealed the orderly arrangement of granules of the semi-crystallinebreadfruit starch was disrupted on gelatinization. The viscosity and flow of pregelatinized starchwere enhanced. Theophylline microbeads were near spherical in shape with size range 1.09± 0.672 to 1.58 ± 0.54 mm. FTIR and XRD spectra confirmed there was no drug-polymerinteraction. Microsphere size, swelling increased while entrapment and dissolution time (t50)reduced with polymer: drug ratio. The entrapment efficiency ranged from 30.99 ± 1.32 to 78.50± 2.37%. Optimized formulation, starch: alginate ratio 3:1 at polymer: drug ratio of 2:1, gave aprolonged dissolution time (t50 = 8.40 ± 1.20 h).Conclusion: Breadfruit starch was suitable as a copolymer for the controlled delivery oftheophylline in microbeads which could serve as a substitute to synthetic polymers in drugdelivery

Pharmaceutical Applications of Pectin

Pectin, a natural ionic polysaccharide found in the cell wall of terrestrial plants undergoes chain–chain association to form hydrogels upon addition of divalent cations. Based on its degree of esterification, pectin has been classified into two main types. The high methoxyl pectin with a degree of esterification greater than 50%, which is mainly used for its thickening and gelling properties and the low methoxyl pectin, which is widely used for its low sugar-content in jams, both applications being in the food industry. Pectin is mostly derived from citrus fruit peels, but can also be found in other plants such as waterleaf leaves, cocoa husk, and potato pulps. Pectin has been used as an excipient in pharmaceutical formulations for various functions. This chapter will focus on the various applications to which pectin has been used in the pharmaceutical industry