HPMC E5 Research Articles

Design and In vivo Evaluation of Palonosetron HCl Mouth Dissolving Films in the Management of Chemotherapy-Induced Vomiting

Fast dissolving oral delivery systems are solid dosage forms, which disintegrate or dissolve within 1 minute in the mouth without drinking water or chewing. Mouth dissolving film (MDF) is a better alternate to oral disintegrating tablets due to its novelty, ease of use and the consequent patient compliance. The purpose of this work was to develop mouth dissolving oral films of palonosetron HCl, an antiemetic drug especially used in the prevention and treatment of chemotherapy-induced nausea and vomiting. In the present work, the films were prepared by using solvent casting method with various polymers HPMC E3, E5 & E15 as a film base synthetic polymer, propylene glycol as a plasticizer and maltodextrin and other polymers. Films were found to be satisfactory when evaluated for thickness, in vitro drug release, folding endurance, drug content and disintegration time. The surface pH of all the films was found to be neutral. The in vitro drug release of optimized formulation F29 was found to be 99.55 ± 6.3 7% in 7 min. The optimized formulation F29 also showed satisfactory surface pH, drug content (99.38 ± 0.08 %), disintegration time of 8 seconds and good stability. FTIR data revealed that no interaction takes place between the drug and polymers used in the optimized formulation. In vitro and in vivo evaluation of the films confirmed their potential as an innovative dosage form to improve delivery and quick onset of action of Palonosetron Hydrochloride. Therefore, the mouth dissolving film of palonosetron is potentially useful for the treatment of emesis disease where quick onset of action is desired, also improved patient compliance.

FABRICATION AND OPTIMIZATION OF NOVEL GLIPIZIDE SUSTAINED RELEASE MATRICES FOR SOLUBILITY AND DISSOLUTION ENHANCEMENT BY SOLID DISPERSION THROUGH HYDROPHILLIC CARRIERS

The present research work was to improve the dissolution rate of glipizide which belongs to BCS II drug by enhancing its aqueous solubility using different hydrophilic carriers like PEG 6000 and hydroxypropyl methylcellulose E15 (HPMC E15). The solid dispersion was embedded into the matrix of polymers to sustain the release pattern of drug. The various solid dispersion formulations were prepared by employing fusion method using different carriers. Further solid dispersion formulations were subjected to different in-vitro evaluation tests for solubility, drug content uniformity, drug-polymer interaction, DSC study and in-vitro drug release study. Tablets were prepared by direct compression method and evaluated for various physical parameters. A direct compression method using response surface methodology, followed by optimization of the evaluated parameters was employed to get the final optimized formulation. The results of drug content uniformity showed the uniform dispersion of glipizide in solid dispersion formulations. The DSC endothermic peak at 216.08°C due to glipizide was partially and completely disappeared in solid dispersion formulation indicating that drug was completely dispersed in formulations. In-vitro drug release showed 80.35% in 60 minutes for the best solid dispersion formulation S3 (ratio 1:3). Among all the formulations, F4 shows 92.87% better sustained release at the end of 12 hrs. The release co-efficient values ‘n’ (E‚0.5) indicated that the drug release followed fickian diffusion mechanism based on formulation factors. The stability studies were carried out according to ICH guideline and result found of selected formulation was stable.Keywords: Glipizide, Solid dispersion, Xanthan gum, MatricesÂ

DEVELOPMENT AND OPTIMIZATION OF FAST DISSOLVING ORAL FILM CONTAINING ARIPIPRAZOLE

The present investigation was aimed with the objective of developing fast dissolving oral films of Aripiprazole to attain quick onset of action for the better management of Schizophrenia. Fourteen formulations (F1-F14) of Aripiprazole mouth dissolving films by solvent-casting method using HPMC E5, HPMC E15, Maltodextrin, PG and PVA. Formulations were evaluated for their physical characteristics, thickness, folding endurance, tensile strength, disintegration time, drug content uniformity and drug release characteristics and found to be within the limits. Among the prepared formulations F13 showed minimum disintegration time 10 sec, maximum drug was released i.e. 99.49 ± 0.36% of drug within 8 min when compared to the other formulations and finalized as optimized formulation. FTIR data revealed that no interactions take place between the drug and polymers used in the optimized formulation. The in vitro dissolution profiles of marketed product and optimized formulation was compared and found to be the drug released was 20.73 ± 0.25 after 8 min. Therefore, it can be a good alternative to conventional Aripiprazole for immediate action. In vitro evaluation of the Aripiprazole fast dissolving oral films confirmed their potential as an innovative dosage form to improve delivery and quick onset of action of Aripiprazole. The mouth dissolving film is potentially useful for the treatment of Schizophrenia where the quick onset of action is desired.

Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing

Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8h floating process with traditional pharmaceutical excipients and lattice internal structure design.

In Vitro and In Vivo Evaluation of Taste Masked Chlorhexidine-Releasing Oral Films

The present investigation was undertaken with the objective of formulating chlorhexidine diacetate containing fast dissolving oral films to serve as superior alternative to mouthwash, aiming at consumer compliance. Various film forming agents, plasticizers and taste masking agents were evaluated for optimizing the composition of fast dissolving oral films. The potential of arginine hydrochloride as taste masking agent for fast dissolving oral films containing hydroxypropylmethylcellulose E5 (HPMC E5), propylene glycol and sucralose were formulated. Fast dissolving oral films of chlorhexidine diacetate were evaluated for the in vitro dissolution profile and in vitro microbiological assay. Oral films exhibited satisfactory in vitro dissolution profile and in vitro antimicrobial activity. Effect of incorporation of eugenol on the in vivo performance of oral films was evaluated in human volunteers. Arginine hydrochloride and eugenol containing oral films improved effectiveness and acceptability of films with respect to taste masking, mouth feel and mouth freshening without compromising the in vivo dissolution time.

Downstream drug product processing of itraconazole nanosuspension: Factors influencing tablet material properties and dissolution of compacted nanosuspension-layered sugar beads

There has been limited research done on the downstream processing of nanosuspensions into solid oral dosage forms. This paper demonstrates the bead layering process with a layering level at 150% and 240%, as well as the selection and justification of the outer phase excipients for tabletability and disintegrating properties. In a previous study, an itraconazole nanosuspension stabilised by SDS and HPMC E5 was layered onto sugar beads with coating polymer HPMC VLV. In the current study, compression studies with these layered beads utilising the small bead size at 150% or 240% layering levels with outer phase cushioning excipients MCC, copovidone or isomalt were performed. Other excipients such as co-compressed crospovidone-PEG 4000; DCP functioning as a disintegrant; and HPC as a binder was also added. Target output variables were achieved with a balance between an adequate tensile strength and fast dissolution rate with a release of 99.0% (±1.0% SD) within 10min, which is in accordance with the FDA guidance for dissolution testing. The results show that the compaction of nanosuspension-layered beads is a suitable process for processing an itraconazole nanosuspension into a solid dosage form such as a compacted tablet without compromising on drug release.

Formulation and Optimization of Nanosuspension Prepared By Media Milling Technique to Enhance the Solubility of Isradipine

Isradipine is a poorly water soluble antihypertensive drug has low bioavailability. The aim of this study was to formulate and characterize isradipine nanosuspension to enhance the solubility of isradipine and thus its bioavailability. Media milling technique was used for the formulation of nanosuspension. The effects of different important process parameters, i.e. the selection of stirring time, selection of concentration of zirconium beads, stirring speed were investigated by preliminary studies while concentration of stabilizers were optimized by simplex lattice design. Concentration of HPMC E3 LV(X1), Carbopol 934P(X2) and PVP K25(X3) were selected as the independent variables whereas mean particle size (Y1), saturation solubility (Y2) and cumulative percentage drug release (cpr) (Y3) were selected as dependent variables. The optimized batch had 100% w/v of zirconium beads, 0.5%w/v of PVP K25 as stabilizer, 0.1%w/v of isradipine, 15 ml of distilled water and 20 hours of stirring time. The particle size and zeta potential of optimized nanosuspension were 248.6 ± 20 nm and 13.96 ± 5 mV respectively. The size of particles of nanosuspension was measured by particle size analyser and transmission electron microscopy (TEM). Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) analysis indicated that there was no interaction between drug and stabilizers. The saturation solubility and in vitro dissolution rate of isradipine was significantly increased by particle size reduction and which may leads to increase the bio-availability of the Isaradipine. The stability study of the formulation was carried out for a period of 12 months.

Formulation of clarithromycin floating microspheres for eradication of Helicobacter pylori

The aim of this study was to develop floating microspheres for gastroretentive delivery of clarithromycin for eradication of Helicobacter pylori. The microspheres were prepared by solvent evaporation using ethyl cellulose (EC) at different weight ratio with clarithromycin with hydroxypropyl methyl cellulose (HPMC E5) acting as secondary polymer. The emulsifier employed either polyvinylpyrrolidone (PVP) or polyvinyl alcohol (PVA). The microspheres were evaluated for floatation, drug entrapment and release, particle size, shape and surface morphology. The physical form of clarithromycin was monitored using FTIR, DSC and X-ray diffraction. The microspheres were in micron range with particle size reducing when replacing PVP with PVA. Further size reduction was recorded in presence of HPMC. The entrapment efficiency increased at high EC concentration especially in presence of HPMC. Immediate floatation was seen with at least 56% of the particles remaining on the surface after 8 h. Physical characterization reflected amorphousization or solubilization of clarithromycin after entrapment in the microspheres. The release pattern followed Higuchi matrix kinetic model in most formulations except those containing low concentration of EC or those containing high HPMC content with HPMC increasing the rate of drug release. The study presented floating microspheres with different release pattern depending on the composition.

Comparative impact of different binder addition methods, binders and diluents on resulting granule and tablet attributes via high shear wet granulation

This study investigated comparative impact of different binder addition methods (pouring, dripping, spraying), binders and diluents on resulting granule and tablet attributes via high shear wet granulation. Lactose monohydrate and mannitol as diluents, and hydroxypropyl methylcellulose (HPMC E5) and polyvinylpyrrolidone (PVP K30) as binders were used. Granules were characterized for morphology, bulk-density, tapped-density, flow, size, segregation-potential and friability. To determine granule friability, procedure described in European Pharmacopoeia was slightly modified to reduce manual-variations and obtain appreciable discrimination between the formulations. Binder-diluent affinity was assessed by measuring contact angles of diluent-dispersion droplets on binder films over a period of time. All blends were pressed at the same compression force and resulting tablets were characterized for pharmacotechnical properties. Results revealed that the binder addition methods altered granule-shape, which predominantly governed the granule flow. The binder addition by spraying increased fines, blend segregation-potential, granule friability, tablet tensile-strength and tablet disintegration-time; binder addition by pouring showed an opposite impact. Mannitol granules exhibited lower bulk density, superior flow, lower segregation-potential and higher friability than their lactose counterparts. Amongst binders, PVP produced more friable granules compared to HPMC. The high polydispersity-index of polymer-binder induced non-homogeneity facilitating the blend segregation-potential. Due to higher affinity, HPMC was suitable binder for mannitol, and PVP for lactose to promote granule growth. The binder-diluent affinity dominated viscosity and surface tension of binder solution to improve granule size. Increase in granule size decreased granule-friability, which subsequently decreased tablet hardness, tensile-strength and disintegration-time. Mannitol produced harder tablets, and lactose tablets disintegrated faster by all binders and binder addition methods.

Development of Salbutamol Sulphate Sublingual Films in Pullulan Matrix for Enhanced Bioavailability & Clinical Efficacy.

Salbutamol sulphate (SS) is a model short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm having poor bioavailability (50%) due to its extensive first-pass effect. Formulation of SS as fast dissolving sublingual films (FDSFs) using a biocompatible and biodegradable Pullulan polymer to bypass its metabolism in liver and offers a fast relieve of asthma. Films were prepared by solvent casting technique adopting 32 factorial design to study the effect of two independent variables namely; polymer type (HPMC E5, Pullulan, and L-HPC) and polymer to Maltodextrin ratio (3:0, 3:1 or 5:1). Films physicomechanical properties, disintegration time and in-vitro dissolution of the prepared formulations were evaluated. Formula F3 containing Pullulan with Maltodextrin in a ratio 3:1 has the least disintegration time (26±2.6 seconds) and the highest dissolution rate (100%±0.5%) after four minutes. Pharmacokinetic study of the optimum formula F3 in healthy human volunteers revealed a shorter tmax (0.75±0.25 hour) compared to Ventolin® tablet 2 mg (2.1±0.37 hour). Clinical evaluation of F3 in 14 male asthmatic patients using ZAN Spirometry showed clinical improvement in lung function parameters when compared with Ventolin® tablets. FDSFs significantly improved the bioavailability of SS and resulted in dramatic improvement in its clinical efficacy.

Evaluation of Mechanical Properties of Nonsteroidal Anti-Inflammatory Matrix Type Transdermal Therapeutic Systems

Abstract Objective: Transdermal therapeutic systems (TTSs) represent an intensely studied alternative to oral delivery of non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of rheumatic diseases due to its ability of avoiding the side effects of the oral route. This study aims to present the evaluation of the mechanical properties of three NSAIDs (meloxicam, tenoxicam and indomethacin) individually included in four type of polymeric matrixes, as part of new formulations development process. Methods: 12 products in form of TTS matrixes were prepared by solvent casting evaporation technique, using hydroxypropyl methylcellulose (HPMC 15000, HPMC E5) and/or ethylcellulose as matrix-forming polymers. Each of the resulted products was evaluated by determining the water vapor absorption, desorption or transmission in controlled atmosphere humidity (evaluation of porosity); the elongation capacity, tensile strength and bioadhesiveness (evaluation of mechanical properties). Results: The analysis of three groups of the experimental data expressed as averages on each group was necessary, in order to identify the parameters which statistically are critically influenced by the ingredients associated in the TTSs matrix compositions. Analysis by normality tests, variance and correlation tests (Anova, Pearson) enabled evaluation of the effect of NSAID type vs. the effect of polymer matrix type on the parameters of the NSAID TTS matrix. Conclusions: Meloxicam incorporated in the structure of HPMC 15000 polymeric matrix favors its viscoelastic structure. Ethylcellulose functions as plasticizer and supports the matrix bioadhesiveness. HPMC E5 does not meet the requirements for TTS preparation in the used experimental conditions.

Optimization of film-coating formulation containing a novel low molecular weight hypromellose to achieve balanced tablet-coating performance

In recent years, a novel low molecular weight hypromellose (hypromellose 2906, VLV hypromellose) was developed to improve tablet-coating process and lower costs in the pharmaceutical industry. Such VLV hypromellose imparted economic, environmental, and performance benefits to the coating process and final products. However, there were still some concerns about this polymer in regard to weak mechanical strength of films and resultant stability issues of film coatings on tablets. In this study, a tablet-coating formulation was optimized using Box–Behnken design via blending conventional hypromellose with VLV hypromellose to achieve balanced coating performance in terms of highly productive coating, no sticking issues under mild coating conditions, and robust tablet film coatings in an accelerated stability study. By addition of only 5 wt% of conventional hypromellose (3.35 wt% HPMC E50 and 1.65 wt% HPMC E3), the film elongation and toughness index of optimized VLV hypromellose formulation increased by 154% and 372%, respectively, while the solution viscosity was still suitable for spray coating. The results of the following tablet-coating trials and stability study revealed that the stability and quality of tablet film coatings were significantly improved using this optimized VLV hypromellose-coating formulation, while a highly productive coating process and mild coating conditions without “sticking” issues were maintained simultaneously to the utmost extent.

Formulation Development and Optimization of Oral Thin Films of Zolpidem Tartarate

<em>The aim of the present study was to formulate and evaluate oral thin films of zolpidem tartarate. Zolpidem tartarateis used to treat insomnia. It affects chemicals in your brain that may become unbalanced and cause sleep problems (insomnia). Zolpidem tartarate oral thin films were prepared by using solvent casting method. In this method, water soluble polymer is completely dissolved in to form uniform clear viscous solution other ingredients including API are dissolved in a small portion of aqueous solvent by using a high shear processor. This viscous solution is degassed under the vacuum to remove the air bubbles. This bubble free solution is poured into a glass mold and kept in oven at 40 º-50ºC. Oral disintegrating films are prepared using three grades of polymers HPMC E5, GUAR GUM and SODIUM ALGINATE Compatibility of Zolpidem tartarate with polymers was confirmed by FT-IR studies. All the formulations were evaluated for their physical appearance, average weight and thickness, folding endurance, disintegration time, tensile strength, percentage elongation, drug content, content uniformity and in vitro drug dissolution studies. From the result, it was concluded that the fast dissolving films of Zolpidem tartarate can be made by solvent casting technique with enhanced dissolution rate and taste masking by using suitable combination of sweeteners, flavors and citric acid. The final composition optimized was drug to Guar Gum ratio of 1:1, plasticizer concentration of 15% w/w of polymer. The film had acceptable physical properties, assay and uniformity values and in vitro dissolution within 2 minutes.</em>

Nanodispersion-loaded mucoadhesive polymeric inserts for prolonged treatment of post-operative ocular inflammation

Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded nanodispersion aiming the sustained delivery of the drug to the cornea have been developed and characterised for the treatment of post-operative ocular inflammation. Nanodispersions were prepared by ionic gelation method with various concentrations of chitosan and sodium tripolyphosphate. The developed nanodispersions were analysed for morphology, particle size, dispersion homogeneity, zeta potential, entrapment efficiency and drug release. The nanodispersion that showed the smallest particle size and the highest entrapment efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m films. The formulation with optimum physicomechanical properties was selected to study its ex vivo transcorneal permeation through freshly excised bovine cornea in comparison with the nanodispersion and the marketed eye drops (Acular®). The polymeric ocular film showed greater permeation than aqueous eye drops. Moreover, the ocular film revealed a prolonged anti-inflammatory effect compared to eye drops when applied to inflamed rabbit’s eyes.

Solidification of cinnarizine self-nanoemulsifying drug delivery systems by fluid bed coating: optimization of the process and formulation variables.

Self-nanoemulsifying drug delivery systems (SNEDDS) offer an efficient choice to improve the poor dissolution and erratic bioavailability of poorly-water soluble drugs. However, liquid SNEDDS experience some manufacturing and stability limitations. To overcome these limitations, the current study aims to investigate and optimize the solidification of cinnarizine (CN) liquid SNEDDS onto pellets by fluid bed coating. The study involved optimization of process and formulation variables. The coated self-nanoemulsifying pellets (SNEP) were characterized, their droplet size and dissolution profiles were compared to the corresponding liquid SNEDDS. Higher spray/microclimate air pressure led to minimal agglomeration and minimal spray drying. However, slight increase in inlet air volume above 35 m3/h led to extensive spray drying. The optimized coating formula included oleic acid/Imwitor308/Cremophor El (25/25/50) as liquid SNEDDS, HPMC E3 as coating polymer and Plasacryl™T20 as anti-tacking agent. The optimum concentration of coating solution was 15% and optimum SNEDDS proportion in the coating layer was 40%. The droplet size of reconstituted SNEP was significantly (p < 0.05) higher than liquid SNEDDS, yet the SNEP aqueous dispersion was still within the nano-metric scale. Pure CN showed sharp precipitation upon shifting the media from pH 1.2 to 6.8. In contrast, Both SNEP and liquid SNEDDS maintained >85% CN in solution, even at pH 6.8. Therefore, CN-SNEP seems to be an excellent dosage form that maintains the solubilization benefits of liquid SNEDDS, overcomes their limitations along with the additional benefits of solid dosage form.

Enhanced oral bioavailability and diminished food effect of lurasidone hydrochloride nanosuspensions prepared by facile nanoprecipitation based on dilution

The aim of this study was to improve the oral bioavailability and diminish the food effect of a poorly soluble drug with pH-dependent solubility, lurasidone hydrochloride (LH), by fabricating its nanosuspensions using a facile nanoprecipitation method. Upon dilution with water, LH dissolved in pH4 solution formed growing cores and aggregated into nanoparticles, due to the maximum solubility of LH at pH4. Compared with the batches prepared with other stabilizers, the LH nanosuspensions (LH-NS) stabilized by HPMC E50 were found more stable and had a smaller particle size. A Box-Behnken design (BBD) was used to optimize the critical process and formulation parameters. Then the optimized LH-NS were lyophilized with 1% (w/v) mannitol for long-term stability. According to differential scanning calorimetry and X-ray diffraction analysis, the nanocrystals were still in crystalline state after the preparation procedure. Good physical stability was observed for nanoparticles kept for 6months at 25°C and 40°C/75% RH. The in vitro dissolution rate of LH was significantly increased by reducing the particle size. The in vivo test demonstrated that the Cmax and AUC0–24h values of nanocrystals in fasted rats were approximately 2.08-fold and 2.39-fold greater than that of raw drug, respectively. Besides, there was no significant difference in the oral bioavailability of nanoparticles between fasting and feeding. This nanoprecipitation technique is a promising method with a facile process and avoidance of toxic organic solvents and undesired byproducts for oral delivery of poorly soluble drugs with pH-dependent solubility.

Solubility Enhancement of a BCS Class II Drug Using Granulated Fumed Silica as an Adsorbent

Aim: The aim of this study was to improve solubility and dissolution characteristics of Ibuprofen using granulated fumed silica (Aeroperl®300) as a carrier. Methods: Ibuprofen-silica complex was prepared by solvent evaporation technique using ethanol as the solvent. Formulation I and II consisted of polymers hydroxypropyl methylcellulose (HPMC E5) and Polyvinyl Pyrrolidone (PVP K-30) respectively. Each formulation was prepared using 1:1:1 and 1:1:2 ratio of drug, polymer and silica. Dried powder obtained was characterized using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and Polarized Light Microscopy (PLM). In-vitro dissolution studies were carried out using three different media including Phosphate buffer (pH 6.8), 0.1N Hydrochloric Acid (pH 1.2) and de-ionized water. Results: Drug loading up to 30% w/w was successfully achieved with 1:1:1 ratio formulations. Physical characterization data confirmed change of crystalline Ibuprofen into amorphous form after processing. Maximum solubility increment of 33-37% was achieved in Phosphate buffer with formulations II A and II B within the first 5 minutes of dissolution as compared to the control (pure drug). Conclusion: Enhancement in drug solubility and subsequent dissolution rate can be attributed to adsorption of amorphous drug molecules onto porous silica that readily desorb on contact with dissolution media. High porosity and huge surface area of silica makes it a potential candidate for improving delivery of poorly soluble drugs.

Formulation of cilostazol spherical agglomerates by crystallo-co-agglomeration technique and optimization using design of experimentation.

Introduction:Spherical agglomeration is one of the novel techniques for improvement of flow and dissolution properties of drugs. Cilostazol is a biopharmaceutics classification system Class II drug with poor solubility resulting in limited bioavailability. The present study aims at improving the solubility and dissolution of cilostazol by crystallo-co-agglomeration technique.Materials and Methods:Cilostazol agglomerates were prepared using various polymers with varying concentration of hydroxypropyl methylcellulose E 50 (HPMC E50), polyvinyl pyrrolidone K30 (PVP K30), and polyethylene glycol 6000. The influence of polymer concentration on spherical agglomerate formation was studied by 32 factorial design. Cilostazol agglomerates were evaluated for percent yield, mean particle size, drug content, aqueous solubility, and in vitro dissolution and further characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD).Results:The agglomeration process resulted in optimized formulation, F3 with mean agglomerate size of 210.0 ± 0.56 μm, excellent flow properties, approximately 15-fold increase in solubility than pure cilostazol and complete drug release in 60 min. Process yield, agglomerate size, and drug release were affected by amount of PVP K 30 and HPMC E50. The presence of drug microcrystal was confirmed by SEM, whereas FTIR study indicated no chemical change. Increase in drug solubility was attributed to change of crystalline drug to amorphous form that is evident in DSC and XRD.Conclusion:Crystallo-co-agglomeration can be adopted as an important approach for increasing the solubility and dissolution of poorly soluble drug.

Formulation and Evaluation of Mucoadhesive Buccal Tablets of Curcumin and its Bioavailability Study

Aim: The main objective of the present work is to improve the bioavailability of curcumin by buccal route and to study in-vitro and in-vivo drug release. Materials and Methods: The mucoadhesive buccal tablets were formulated by direct compression method using hydrophilic polymers such as guar gum, xanthan gum, HPMC E15 in different concentration and piperine as permeation enhancers (1%). Ethylcellulose is used as backing layer to promote the unidirectional flow of drug in the buccal region. Curcumin has a number of beneficial activities, such as potent antioxidant, anti-inflammatory, anticancer, anti-rheumatic and anti-diabetic. When Curcumin is administered orally it has low bioavailability because of poor absorption, rapid GIT metabolism and hepatic first pass metabolism. Curcumin has poor aqueous solubility and better lipid solubility, and buccal region consist of lipid, so the absorption of curcumin can be increased by this route. Results and Discussion: The FT-IR spectra of pure drug with different polymers showed no shift in peak, indicating absence of interaction. The prepared formulations were evaluated for pre-compression studies such as bulk density, tapped density, angle of repose. The post-compressions studies such as weight variation, thickness, friability, hardness, mucoadhesive strength, drug content, swelling studies, in-vitro diffusion studies and in-vitro dissolution studies. Conclusion: All the prepared formulations were within the standard Pharmacopoeial limit. The formulation (FX2) containing xanthan gum showed the best dissolution (97.75%) within 4.0 hours and it follows higuchi model. The in-vivo animal study showed the better bioavailability by buccal route when compare to oral route.

The Flow-Through Cell as an In Vitro Dissolution Discriminative Tool for Evaluation of Gliclazide Solid Dispersions

Gliclazide (GLZ) is used to treat type II diabetes mellitus. It is a poorly soluble drug with variable bioavailability. The aim of this study was to improve GLZ solubility and dissolution rate by mixing or co-grinding with different polymers (PEG 4000, PEG 8000, MCC, HPMC E15 and alginates). Dissolution of two commercial products was carried out for comparison. GLZ solubility in phosphate buffer (pH 7.4) showed that grinding of GLZ considerably increased its solubility while, other polymers did not affect GLZ solubility. Flow-through cell (FTC) dissolution apparatus with two patterns of GLZ powder loading were utilized to achieve sensitive and reproducible dissolution data. The results revealed that distribution of untreated and ground GLZ powder with large volume of glass beads gave the best dissolution profiles in terms of rapid onset of dissolution (Q5min) and dissolution efficiency (DE60min). The best excipient among all was PEG (4000 and 8000), where GLZ physical mixture (PM) enhanced the dissolution rate without co-grinding to form solid dispersion (CSD). The highest dissolution rate and extent were obtained from GLZ:PEG 4000 (1:5) PM, where about 45.88 % were dissolved after 5 min and DE60min was 74.18%.