Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets

The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating tablet (RDT) of the taste-maske drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8∶2 did not show drug release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1∶1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t₉₀, 60 seconds) in SGF compared with marketed formulation (t₉₀, 240 seconds;P<.01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity. Published: June 22, 2007     

Development and Evaluation of Cetirizine HCl Taste-Masked Oral Disintegrating Tablets

The purpose of the current study was to mask the taste of cetirizine HCl and to incorporate the granules produced in oral disintegrating tablets (ODT). The bitter, active substance was coated by fluidized bed coating using Eudragit® RL30-D at levels between 15% and 40% w/w. The ODTs were developed by varying the ratio of superdisintegrants such as sodium croscarmellose, crospovidone grades and low substituted hydroxypropyl cellulose (L-HPC). A direct compression process was used to compress the ODTs under various compaction forces to optimize tablet robustness. The properties of the compressed tablets including porosity, hardness, friability and dissolution profiles were further investigated. The in vitro and in vivo evaluation of the tablet disintegration times showed almost identical rapid disintegration below 10 s at the optimal levels of each superdisintegrant. Finally, the taste and sensory evaluation in human volunteers demonstrated excellence in masking the bitter active and tablet palatability.     

Optimization Studies on Design and Evaluation of Orodispersible Pediatric Formulation of Indomethacin

In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2³ factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology and kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin and various excipients used in the tablet formulation. Stability studies carried out as per ICH Q₁ A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming and disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.     

Disintegration of Highly Soluble Immediate Release Tablets: A Surrogate for Dissolution

The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria. The opinions expressed in this work are only of authors and do not necessarily reflect the policy and statements of the FDA.     

Formulation and Optimization of Orodispersible Tablets of Diazepam

Diazepam is one of the most prescribed benzodiazepines. The purpose of the present research was to optimize the formulation of orodispersible tablets of diazepam. Orodispersible tablets of diazepam were prepared using different types of superdisintegrants (Ac-Di-Sol, sodium starch glycolate, and crospovidone (CP)) and different types of subliming agents (camphor and ammonium bicarbonate (AB)) at different concentrations and two methods of tablets preparations (wet granulation and direct compression methods). The formulations were evaluated for flow properties, wetting time, hardness, friability, content uniformity, in vivo disintegration time (DT), release profiles, and buccal absorption tests. All formulations showed satisfactory mechanical strength except formula F5 which contains camphor and formula F9 which is prepared by direct compression method. The results revealed that the tablets containing CP as a superdisintegrant have good dissolution profile with shortest DT. The optimized formula F7 is prepared using 10% CP as a superdisintegrant and 20% AB as a subliming agent by wet granulation method which shows the shortest DT and good dissolution profile with acceptable stability. This study helps in revealing the effect of formulation processing variables on tablet properties. It can be concluded that the orodispersible tablets of diazepam with better biopharmaceutical properties than conventional tablets could be obtained using formula F7.     

Meloxicam Taste-Masked Oral Disintegrating Tablet with Dissolution Enhanced by Ion Exchange Resins and Cyclodextrin

The purpose of this study was to develop taste-masked oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin, to mask the bitter taste and enhance drug dissolution. Meloxicam (MX) was selected as a model drug with poor water solubility and a bitter taste. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-β-cyclodextrin (HPβCD) or MX/HPβCD complexes, and a mixture of resinate and MX/HPβCD complexes) were made and tablets were prepared by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste, and stability. The results showed that thickness, diameter, weight, and friability did not differ significantly for all of these formulations. The tablet hardness was approximately 3 kg/in.², and the friability was less than 1%. Tablets formulated with resinate and the mixture of resinate and MX/HPβCD complexes disintegrated rapidly within 60 s, which is the acceptable limit for ODTs. These results corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HPβCD complexes provided complete MX dissolution and successfully masked the bitter taste of MX. In addition, this tablet was stable at least 6 months. The results from this study suggest that the appropriate combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste of drug and enhance the dissolution of drugs that are weakly soluble in water.     

Development and Evaluation of Artemether Taste Masked Rapid Disintegrating Tablets with Improved Dissolution Using Solid Dispersion Technique

The purpose of this research was to mask the intensely bitter taste of artemether (ARM) and to formulate a rapid-disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by solid dispersion with mono amino glycyrrhyzinate pentahydrate (GLY) by solvent evaporation method. To characterize and formulate taste masked rapid disintegrating tablets (RDTs) of ARM, the 1:1M solid dispersion was selected based on bitterness score. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. RDTs were evaluated for weight variation, disintegration time, hardness and friability. In vitro drug release studies were performed for RDTs at pH 1.2 and 6.8. Bitterness score was evaluated using mini-column method and compared with gustatory sensation test. FTIR spectroscopy and DSC showed no interaction while XRPD showed amorphization of ARM in GLY solid dispersion. RDTs prepared using solid dispersion, (RDT3), showed faster disintegration (within 28 s) and complete bitter taste masking of ARM. In addition, RDT3 exhibited better dissolution profile at both pH 1.2 and 6.8, than RDTs prepared from pure ARM (RDT5). Taste evaluation of RDTs in human volunteers rated tasteless with a score of 0 to RDT3 and 3 to RDT5. Mini-column revealed that RDT5 showed increase in number of persons who sensed bitterness with increased amount of ARM release while RDT3 sensed no bitterness. Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity with improved dissolution.     

Development of Orodispersible Films Containing Benzydamine Hydrochloride Using a Modified Solvent Casting Method

The aim of this study was to develop benzydamine hydrochloride-loaded orodispersible films using the modification of a solvent casting method. An innovative approach was developed when the drying process of a small-scale production was used based on a heated inert base for casting the film. During this process, two types of film-forming maltodextrins for rapid drug delivery were used. They were plasticized with two different polyols (xylitol and sorbitol). Superdisintegrant Kollidon® CL-F was tested as an excipient that can induce faster disintegration of the prepared films. The influence of the formulation parameters (dextrose equivalent of film-forming maltodextrins, a type of plasticizer, and the presence of superdisintegrant) on the disintegration time, mechanical properties, and moisture content of films was statistically evaluated using a multivariate data analysis. Orodispersible films containing maltodextrin with lower dextrose equivalent value showed better mechanical properties (tensile strength ranged from 886.6?±?30.2 to 1484.2?±?226.9 N cm^?2), lower moisture content (0.5?±?0.0 to 1.2?±?0.2%), and shorter disintegration time (17.6?±?2.9 to 27.8?±?2.8 s). Films plasticized with xylitol showed shorter disintegration time (17.6?±?2.9 to 29.2?±?3.8 s) than films containing sorbitol (23.8?±?2.9 to 31.7?±?3.9 s). With the addition of superdisintegrant Kollidon® CL-F, a significant influence on disintegration time was not observed. The modified solvent casting method shows great promise in a small-scale laboratory production of orodispersible films, e.g., in a pharmacy lab.     

Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression

Orally disintegrating tablets (ODTs) are challenged by the need for simple technology to ensure good mechanical strength coupled with rapid disintegration. The objective of this work was to evaluate microwave-assisted development of ODTs based on simple direct compression tableting technology. Placebo ODTs comprising directly compressible mannitol and lactose as diluents, super disintegrants, and lubricants were prepared by direct compression followed by exposure to >97% relative humidity and then microwave irradiation for 5 min at 490 W. Placebo ODTs with hardness (>5 kg/cm²) and disintegration time (<60 s) were optimized. Palatable ODTs of Lamotrigine (LMG), which exhibited rapid dissolution of LMG, were then developed. The stability of LMG to microwave irradiation (MWI) was confirmed. Solubilization was achieved by complexation with beta-cyclodextrin (β-CD). LMG ODTs with optimal hardness and disintegration time (DT) were optimized by a 2³ factorial design using Design Expert software. Taste masking using sweeteners and flavors was confirmed using a potentiometric multisensor-based electronic tongue, coupled with principal component analysis. Placebo ODTs with crospovidone as a superdisintegrant revealed a significant increase in hardness from ～3 to ～5 kg/cm² and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/cm², DT?<?30s, and rapid dissolution of LMG, and good stability was optimized by DOE and the design space derived. While β-CD complexation enabled rapid dissolution and moderate taste masking, palatability, which was achieved including flavors, was confirmed using an electronic tongue. A simple step of humidification enabled MWI-facilitated development of ODTs by direct compression presenting a practical and scalable advancement in ODT technology.     

Effects of plantain and corn starches on the mechanical and disintegration properties of paracetamol tablets

The effects of plantain starch obtained from the unripe fruit of the plantMusa paradisiaca L. (Musaceae) on the mechanical and disintegration properties of paracetamol tablets have been investigated in comparison with the effects of corn starch BP using a 2³ factorial experimental design. The individual and combined effects of nature of starch binder (N), concentration of starch binder (C), and the relative density of tablet (RD) on the tensile strength (TS), brittle fracture index (BFI), and disintegration time (DT) of the tablets were investigated. The ranking of the individual effects on TS was RD>C≫N, on BFI was C≫RD>N and on DT was N>C>RD. The ranking for the interaction effects on TS and DT was N-C≫N-RD>C-RD, while that on BFI was N-C≫C-RD>N-RD. Changing nature of starch from a “low” (plantain starch) to a “high” (corn starch) level, increasing the concentration of starch binding agent from 2.5% to 10.0% wt/wt, and increasing relative density of the tablet from 0.80 to 0.90, led to increase in the values of TS and DT, but a decrease in BFI. Thus, tablets containing plantain starch had lower tensile strength and disintegration time values than those containing corn starch, but showed better ability to reduce the lamination and capping tendency in paracetamol tablet formulation. The interaction between N and C was significantly (P<.001) higher than those between N and RD and between C and RD. There is therefore the need to carefully choose the nature (N) and concentration (C) of starch used as binding agent in tablet formulations to obtain tablets of desired bond strength and disintegration properties. Furthermore, plantain starch could be useful as an alternative binding agent to cornstarch, especially where faster disintegration is required and the problems of lamination and capping are of particular concern. Published: October 22, 2005     

Neem Gum as a Binder in a Formulated Paracetamol Tablet with Reference to Acacia Gum BP

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr’s index, Hausner’s ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength–friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.     

Preparation and Evaluation of Orally Disintegrating Tablets Containing Taste-Masked Microcapsules of Berberine Hydrochloride

The purpose of this study was to prepare and evaluate a taste-masked berberine hydrochloride orally disintegrating tablet for enhanced patient compliance. Taste masking was performed by coating berberine hydrochloride with Eudragit E100 using a fluidized bed. It was found that microcapsules with a drug–polymer ratio of 1:0.8 masked the bitter taste obviously. The microcapsules were formulated to orally disintegrating tablets and the optimized tablets containing 6% (w/w) crospovidone XL and 15% (w/w) microcrystalline cellulose showed the fastest disintegration, within 25.5 s, and had a pleasant taste. The dissolution profiles revealed that the taste-masked orally disintegrating tablets released the drug faster than commercial tablets in the first 10 min. However, their dissolution profiles were very similar after 10 min. The prepared taste-masked tablets remained stable after 6 months of storage. The pharmacokinetics of the taste-masked and commercial tablets was evaluated in rabbits. The C_max, T_max, and AUC₀₋₂₄ values were not significantly different from each other, suggesting that the taste-masked orally disintegrating tablets are bioequivalent to commercial tablets in rabbits. These tablets will enhance patient compliance by masking taste and improve patients’ quality of life.KEY WORDS: berberine hydrochloride, microcapsule, orally disintegrating tablet, taste masking     

Preparation and assessment of novel coprocessed superdisintegrant consisting of crospovidone and sodium starch glycolate: A technical note

Summary and Conclusion  Coprocessed superdisintegrant consisting of crospovidone and SSG exhibited good flow and compression characteristics. Cefixime trihydrate and ibuprofen tablets containing coprocessed superdisintegrant exhibited quick disintegration and improved drug dissolution. Publshed: February 2, 2007     

Acid-treated yeast cell wall as a binder displaying function of disintegrant

This investigation examined the application of acid-treated yeast cell wall (AYC) as a binder functioning as a disintegrant. Acetylsalicylic acid (ASA) was granulated with AYC, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), or pullulan (PUL) and compressed into a tablet in the absence of disintegrant. Particle size and angle of repose of the granules, tensile strength, disintegration time, and water absorption behavior of the tablets and ASA release profiles from the tablets were measured. The surface of AYC-granules was observed with a scanning electron microscope. As was the case with the granules of HPC, PVP, or PUL, D50 of the granules of AYC increased with increasing AYC addition percentage, indicating that it is possible to granulate ASA with AYC. Tablets incorporating HPC, PVP, and PUL failed to disintegrate within 30 minutes at all percentages of binder addition because in the case of the HPC, PVP, or PUL tablets in the dissolution medium, water scarcely penetrated into the inner region of the tablet, causing no disintegration. In the case of the AYC tablets, disintegration was not detected at 3% or less of AYC. When AYC was equal to or greater than 5%, AYC tablets disintegrated in approximately 4 minutes and rapid ASA release from the tablets was observed. These results may have been caused by the following. In the case of the AYC 3% granules, ungranulated aspirin powder remained, but in the case of the AYC 5% granules, ASA powder was granulated and covered with AYC. Water absorption was observed initially; however, a plateau was reached in the case of the AYC 3%-tablet. In contrast, in the cases of the AYC 5% and more tablets, water absorption was greater and increased with time. The angle of repose of the AYC 5% granules was 25.7°, which represented high fluidity. The tablets produced by compressing the granules demonstrated sufficient tensile strength greater than 0.8 MPa. The tablets rapidly disintegrated and rapid ASA release was obtained. AYC functioned as a binder at granulation; additionally, AYC served as a disintegrant in the dissolution of drug from the tablets. These results indicate that AYC affords high utility as a unique pharmaceutical additive possessing contrary functions such as binding and disintegration.     

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use

Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3³ FFD. MCC (X₁, %), mannitol (X₂, %) and Indion 414: Pharmaburst 500 ratio (X₃, ratio) were the factors (independent variables) studied, whereas responses studied (dependent variables) were friability (Y1, %), yield (Y2, %) shape (Y3, roundness) in vitro disintegration time (Y4, seconds). The optimized formulation obtained from FFD was characterized for friability, shape and morphology, in vitro disintegration time, porosity, moisture uptake, in vitro release study and in vivo taste and disintegration time in healthy human volunteers. Randomized, two-treatment, two-sequence, two-period, single dose, crossover sensory evaluation study of taste-masked melt-in-mouth pellet was carried out in 10 healthy human subjects. A statistically significant polynomial mathematical relationship was generated between the factors and responses to obtain an optimized formulation. The optimized formulation was characterized (in vitro and in vivo) and exhibited a rapid drug release in vitro attributed to fast disintegration of pellets and high solubility of drug in 0.1 N HCl and buffer (pH 6.8). In vivo, 40% of volunteers ranked taste-masked optimized formulation as slightly bitter while 60% ranked it as no taste. The optimized pellets were conveniently administered in volunteers and exhibited rapid in-vivo disintegration in the oral cavity. Melt-in-mouth pellets can be a used as a platform technology for administering drugs to paediatric patients accurately and conveniently resulting in patient compliance.     

Response Surface Methodology to Optimize Novel Fast Disintegrating Tablets Using β Cyclodextrin as Diluent

The objective of this work was to apply response surface approach to investigate main and interaction effects of formulation parameters in optimizing novel fast disintegrating tablet formulation using β cyclodextrin as a diluent. The variables studied were diluent (β cyclodextrin, X ₁), superdisintegrant (Croscarmellose sodium, X ₂), and direct compression aid (Spray dried lactose, X ₃). Tablets were prepared by direct compression method on B2 rotary tablet press using flat plain-face punches and characterized for weight variation, thickness, disintegration time (Y ₁), and hardness (Y ₂). Disintegration time was strongly affected by quadratic terms of β cyclodextrin, croscarmellose sodium, and spray-dried lactose. The positive value of regression coefficient for β cyclodextrin suggested that hardness increased with increased amount of β cyclodextrin. In general, disintegration of tablets has been reported to slow down with increase in hardness. However in the present study, higher concentration of β cyclodextrin was found to improve tablet hardness without increasing the disintegration time. Thus, β cyclodextrin is proposed as a suitable diluent to achieve fast disintegrating tablets with sufficient hardness. Good correlation between the predicted values and experimental data of the optimized formulation validated prognostic ability of response surface methodology in optimizing fast disintegrating tablets using β cyclodextrin as a diluent.     

Superior disintegrating properties of calcium cross-linked Cassia fistula gum derivatives for fast dissolving tablets

The present investigation was aimed at evaluating the feasibility of using calcium salts of carboxymethylated (CaCOG) or carbamoylethylated (CaCEG) derivatives of Cassia fistula gum as superdisintegrant while formulating fast disintegrating tablets (FDTs) exhibiting lowest disintegration time (DT) at highest mechanical strength. FDTs prepared with CaCOG (5%, w/w) or CaCEG (5%, w/w) were directly compressible and showed superior disintegrating property due to decreased water sorption time, increased particle packaging index, without any significant change in swelling index and effective pore radius. The mechanisms of superdisintegration suggested that probably the presence of Ca²⁺ resulted in intra and/or inter cross-linked bridges in the CaCOG or CaCEG that supported water transporting system even when the aqueous channels in the FDTs were blocked. Thus, the findings indicated great potential for using CaCOG or CaCEG as superdisintegrants in FDTs with high mechanical strength and low DT.     

Improving the tablet characteristics and dissolution profile of ibuprofen by using a novel coprocessed superdisintegrant: A technical note

Summary and Conclusion  The coprocessed superdisintegrant proved to be superior to the physical blend in terms of flow due to size enlargement. Furthermore, the coprocessed superdisintegrant displayed superiority in terms of crushing strength, disintegration time, and drug dissolution. The advantages of the proposed method are easy adaptability in industry and the possibility of bypassing the existing patents in the ereas of quick disintegration and dissolution. Published: February 16, 2007     

Formulation and Evaluation of Taste Masked Oral Reconstitutable Suspension of Primaquine Phosphate

The purpose of this research was to mask the intensely bitter taste of primaquine phosphate (PRM) and to formulate suspension powder (cachets) of the taste masked drug. Taste masking was done using beta-cyclodextrin. To characterize and formulate taste masked cachets of PRM, the 1:25 M physical mixture was selected based on bitterness score. Phase solubility studies, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Cachets were evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated using gustatory sensation test. Phase solubility studies showed weak interaction between PRM and CD. The FTIR, DSC and XRPD studies indicated inclusion complexation in physical mixture and kneaded system. In addition, kneaded system and physical mixture exhibited better drug release at pH 1.2 and negligible effect at pH 6.8. Cachets prepared using physical mixture, (DS24), showed complete bitter taste masking and easy redispersibility. Taste evaluation of cachets in human volunteers rated tasteless with a score of 0 to DS24 and 3 to DS25. Thus, results conclusively demonstrated successful taste masking and formulation of cachets with taste masked drug.     

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1∶9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3² randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.