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By combining erodible polymer with rupturable polymer lag time increases with increasing weight ratio of HPC-EXF/EC. This is only because while combining hydrophilic HPC-EXF with EC; HPC-EXF acts as a binder too. As tablet comes in the contact of dissolution medium HPC-EXF starts hydrating but as EC is hydrophobic in nature it retards the hydration of HPC-EXF and as EC is semi permeable in nature105 dissolution medium penetrates faster in EC coated tablet compared to along with HPC- EXF. As HPC-EXF forms a compact with EC water would not penetrate faster as compared to EC outer coating shell.
But in formulation S8 to S11 all formulations containing the weight ratio of HPC-EXF/EC is same i. e. 50:50. Change is only in the inner core tablet formulation in each formulation. The formulation S8 to S11 containing core tablet formulations A1 to A4 respectively.
Formulation containing Avicel PH 101 as filler binder, Ac-Di Sol as superdisintegrant in the 1% and 2% for formulation A1 and A2 respectively. Magnesium stearate and aerosil used as lubricant and glidant. As the concentration of Ac-Di-Sol increases show decrease in the disintegration time and increase in dissolution of drug. From drug release it was observed that increase in concentration of Ac- Di-Sol increases the drug release upto 2% concentration in the tablet, but further increase in the concentration of Ac- Di-Sol not show any increase in the dissolution rate.
Formulations A3 and A4 were containing Starlac as filler binder, Ac-Di Sol as superdisintegrant in the 1% and 2% respectively. Magnesium stearate and aerosil were used as lubricant and glidant. As the concentration of Ac-Di-Sol was increases show decrease in the disintegration time and increase in dissolution of drug. 100% drug were released from the all the formulation A1, A2, A3 and A4 in 24, 18, 20, 16 minutes respectively. From drug release it was observed that increase in concentration of Ac- Di-Sol increases the drug release. So the formulation S8, S9, S10 and S11 having same lag time upto 6 hours.
COMBINATION OF ERODIBLE MATERIAL (KLUCEL EXF) WITH INERT HYDROPHOBIC MATERIAL (DI-TAB®) IN DIFFERENT WEIGHT RATIO
In order to investigate effect of excipients on the lag time and drug release rate from HPC-EXF, and DI -TAB® (DCP Dihydrate - an insoluble excipient) were chosen.
When hydrophobic excipients combined with HPC-EXF, the decreased in lag time was also observed with increase in weight ratio of DI -TAB®/HPC-EXF. As DI -TAB® is hydrophobic in nature, it retards the hydration of outer coating layer to the some extent, but once as HPC-EXF hydrates by dissolution medium it starts dissolving and eroded because of compacts formed by HPC-EXF alone is more firm then combination of DI -TAB® with HPC-EXF. Due to rapid hydration and erosion of outer coating layer, no significant effect of core composition observed.
This indicates that both lactose and dicalcium phosphate dihydrates had similar effect on the lag time and release rate of salbutamol sulphate from outer coating layer composed of HPC-EXF. So it can be concluded that hydrophilicity or hydrophobicity of added excipients in the outer core has a little effect on the lag time and release behavior of salbutamol sulphate from outer coating layer. The explanation for the effect of added excipients in the outer shell on the lag time of press coated tablet was that these excipients reduced the tortuosity of the diffusion path of the dissolution medium and increase the erosion of erodible polymer.
The order of the time lag changed according to the weight ratio of HPC-EXF/DI-TAB® mixture as follows: S12 (100:00) 5 hours, S13 (87.5:12.5) 3 hours, S14 (75:25) 3 hours, S15 (50:50) 2 hours, S16 (25:75) 2 hours, S17 (12.5:87.5) 1 hour and S18 (00:100) 1 hour.
COMBINATION OF GELLABLE MATERIAL XANTHAN GUM (XG) WITH HPMC K 100M IN DIFFERENT WEIGHT RATIO
Salsa et al128 studied hydration rate of this synthetic polymer relates to its hydroxypropyl substitutes percentage. HPMC-K100M contains the greatest amount of these groups and produces strongly viscose gel that plays an important role in drug release especially at the beginning of the release profile. Therefore, the quick hydration and subsequent gel formation is a foremost and important property of an excipient for it to be used in sustained-release formulations.
Talukdar et al129 reported in respect of controlled drug release behaviour xanthan gum matrices have some important pharmaceutical as well as economical advantages (e.g., absence of initial burst release, higher drug-retarding ability, more reproducibility in drug release, and the possibility of zero-order release kinetics) over HPMC matrices. Considering the influence of ionic strength of the medium on drug release behaviour xanthan gum has a disadvantage that the drug release is influenced by the total salt concentration within the range of gastro-intestinal tract, while the drug release from HPMC matrices is independent of ionic strength. But this ionic strength dependency should not be considered as a total failure of XG for controlling the drug release. Compaction characteristics between the two polymers are quite similar, but the flowability of xanthan gum is better than that of HPMC.
Talukdar et al130 reported drug diffusion in hydrated HPMC matrices is higher than in hydrated xanthan gum matrices. These differences in drug diffusion between the two polymer solutions well explain the reason for previously observed higher ability of xanthan gum than HPMC to retard the release of a drug when they used as matrix forming agent, for controlled-release drug delivery.
The order of the time lag changed according to the weight ratio of XG/HPMC K100M mixture as follows: S19 (87.5:12.5) 8 hours, S20 (75:25) 7 hours, S21 (50:50) 6 hours, S22 (25:75) 6 hours, S23 (12.5:87.5) 6 hours and S24 (100:00) 7 hours.
EFFECT OF DIFFERENT HPMC GRADES ON DRUG RELEASE PROFILE FROM COATED TABLETS
Wan et al.131 studied release mechanism of drug through hydroxypropylmethylcellulose (HPMC) matrices, showed that the normalized increase in matrix thickness after 30 min of swelling for HPMC matrix tablets was higher for higher molecular weight HPMC grades. They attributed this to the larger hydrodynamic volume occupied by higher molecular weight chains when hydrated. As the polymer chains become more hydrated and the gel becomes more dilute, the 'disentanglement concentration' may be reached, that is, the critical polymer concentration below which the polymer chains disentangle and detach from a gelled matrix. The polymer will then undergo simultaneous swelling, dissolution and diffuse into the bulk medium resulting in erosion of the polymer.
Hypromellose acetate succinate is commonly used in oral pharmaceutical formulations as a film coating, as well as enteric coating material for tablets or granules.132, 133, 134 It is insoluble in gastric fluid but will swell and dissolve rapidly in the upper intestine. For aqueous film coating purposes, a dispersion of hypromellose acetate succinate fine powder and triethyl citrate (as a plasticizer) in water is commonly utilized.135, 136, 137 Organic solvents can also be used as vehicles for applying this polymer as a film coating. Hypromellose acetate succinate may be used alone or in combination with other soluble or insoluble binders in the preparation of granules with sustained drug-release properties; the release rate is pH-dependent. Dispersions of poorly soluble drugs with hypromellose acetate succinate are prepared using techniques such as mechanical grinding, solvent evaporation, and melt extrusion.138, 139, 140, 141, 142
The order of the time lag changed according to the weight ratio of HPC-EXF/DI-TAB® mixture as follows: S25 (100:00) 7 hours, S26 (100:00) 3 hours, S27 (100:00) 5 hours and S28 (100:000) 6 hours.
EFFECT OF DIFFERENT EUDRAGIT GRADES ON DRUG RELEASE PROFILE FROM COATED TABLET
Eudragit L100 and S100 types are used as enteric coating agents because they are resistant to gastric fluid. Different types are available that are soluble at different pH values: e.g. Eudragit L is soluble at pH > 6; Eudragit S and FS are soluble at pH > 7.
The order of the time lag changed according to the coating of different eudragit grades are as follows: S29 (100:00) 5 hours and S30 (100:00) 4 hours.
EROSION STUDY OF PRESS COATED TABLET
Upon increasing weight ratio of EC/HPC-EXF lag time of all subsequent formulations increases and % erosion of tablet decrease, this was just because EC is hydrophobic in nature it would not erode but as HPC-EXF present in it get dissolved and eroded. In formulation containing Starlac® as a filler in core tablet, drug get released when almost complete outer coating shell get eroded, while in formulation containing avicel® as a filler in core tablet drug get release when sufficient internal pressure generate in the core rather than complete erosion of outer coating layer. When formulation shows increase in lag time upon increases in weight ratio of EC/HPC-EXF, the difference was in comparative delay in lag time and greater % erosion. This is because of core tablet present in these formulations were not generate sufficient to internal pressure two broke the outer coating layer at same time point as in case with formulations. And finally it takes more time to get release of drug and % erosion of outer coating layer increases.
Upon increasing weight ratio of HPC-HF/HPC-EXF lag time increases and erosion of final tablet depends upon the lag time of tablet. This is because the Ac-Di-Sol® present in core tablet generate sufficient pressure to broke the outer coating layer, while in formulations, drug get released only when complete erosion of outer coating layer take place. While different correlation of lag time and % erosion of tablet observed in formulations. This is because further increase in weight ratio of HPC-HF/HPC-EXF forms a tight gel structure and the pressure generated in core tablet of formulations were not sufficient to broke the outer coating layer. And also the fillers (avicel®) present in the core tablets of formulations retards the hydration of core. And drug gets only released when dissolution medium completely hydrates the core tablet, this would take long time as compared to formulation containing C1 core tablets.
While Starlac® present in the core tablet of formulations gives rapid drug release by diffusion from the formed gel structure because of concomitance effect of hydration and disintegration of Starlac®.