Hydroxypropyl Methylcellulose E5 Research Articles

Quercetin nanocrystals for bioavailability enhancement: Impact of different functional stabilizers on in vitro/in vivo drug performances.

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro, and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant difference in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC0～t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the Cmax showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with Tmax at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same Tmax at 5.33 h. The longest MRT0～t (11.72 h) and t1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro, oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation.

Enhanced dissolution of curcumin-resorcinol cocrystal by the inhibition effect of HPMCAS on solution-mediated phase transformation

The present study aimed to investigate the inhibition effect of polymers on the solution-mediated phase transformation (SMPT) of cocrystals during dissolution. Curcumin-resorcinol (CUR-RES) cocrystal was prepared by slow solvent evaporation, and the best precipitation inhibitor of curcumin (CUR) was selected from five polymers including hydroxypropyl methylcellulose acetate succinate (HPMCAS), hydroxypropyl methylcellulose (HPMC) E5, HPMC E50, Poloxamer 188 (P188) and polyethylene glycol (PEG) 6000 by solvent-shift precipitation test. Then non-sink dissolution tests and intrinsic dissolution rate (IDR) tests were performed with or without HPMCAS to explore the influence of HPMCAS on the dissolution of the cocrystal. It was showed that HPMCAS could effectively inhibit the crystallization of CUR so that the dissolved drug concentration in a predissolved 0.1 % HPMCAS solution at 2 h was nearly 15 μg/mL, which was at least 150 times higher than that without HPMCAS. The red CUR-RES cocrystal turned gradually to yellow CUR during the dissolution tests in the absence of HPMCAS, while the transformation was prevented in the presence of HPMCAS. The present work fully exploits the solubility advantages of CUR-RES cocrystal via the use of precipitation inhibitor and offers important insights into reducing the risk of SMPT during cocrystal dissolution, which is crucial for the development of pharmaceutical cocrystal formulations.

Optimization of prediction model for personalized water pills based on semantic analysis of traditional Chinese medicine materials

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

Bioadhesive behaviors of HPMC E5: comparative analysis of various techniques, histological and human radiological evidence

Enhancing drug residence duration within the stomach offers distinct advantages for both localized and systemic effects. Numerous strategies have been proposed to extend drug residence time, with mucoadhesive polymers being a notable avenue. In this context, hydroxypropyl methylcellulose E5 has been employed as both a binding agent for granulating contrast metal powder and a mucoadhesive polymer, spanning various concentrations. The in vitro bioadhesion strength of the formulated tablets was gauged against the stomach lining of rabbits, for the quantification of bioadhesive forces. The temporal aspect of bioadhesion was evaluated through two approaches: one centered on gastric fluid dynamics and another proffered by the researchers, focusing on gastric wall kinetics. The results divulged a decline in bioadhesion force concomitant with high polymer concentrations. Histological examination of stained stomach sections revealed mucosal perturbations within the rabbit stomach. These disruptions exhibited an escalating trend in conjunction with elevated polymer concentrations, culminating in extensive disturbance at a 7.5% polymer concentration. The outcomes unveiled a direct relationship between polymer concentration increments and extended contact time. Subsequent radiological tracking of contrast metal behavior within a mature human stomach indicated a residence time of 6 h due to the entrapment of displaced components at disparate locations.

Formulation Development and Evaluation of Mouth Dissolving Film of Taurine and Their Future Perspectives

This study focuses on the formulation development and evaluation of mouth dissolving films (MDFs) containing taurine, an amino acid with potential therapeutic benefits. Taurine-loaded MDFs were formulated using hydroxypropyl methylcellulose (HPMC) E5 as the polymer, polyethylene glycol 400 (PEG 400) as the plasticizer, and sucrose as the sweetening agent. Additional ingredients included menthol for flavoring and citric acid for saliva stabilization. The formulations were evaluated for various parameters including physical appearance, thickness, weight variation, surface pH, in vitro disintegration time, folding endurance, drug content, and in vitro drug release. Results demonstrated uniformity, flexibility, and rapid drug release, with formulation F5 exhibiting the highest drug content and desirable properties. Future perspectives include exploring therapeutic applications, personalized medicine, and regulatory approval for clinical use. This study highlights the potential of taurine MDFs as a patient-friendly dosage form with promising therapeutic efficacy

Development of rapidly soluble mebendazole nanosuspension for colorectal cancer

Mebendazole (MBZ) has been proven as a repurposing molecule against colorectal cancer. Unfortunately, its clinical application is constrained by its extremely poor solubility and bioavailability. The aim of the current work was to augment the dissolution rate at colonic pH and the anticancer efficacy by formulating MBZ nanosuspension (NS). A robust MBZ NS was developed using a combination of Sodium Lauryl Sulphate (SLS) and Hydroxy Propyl Methyl Cellulose E5 (HPMC) as stabilizers through the dual centrifugation method. The prepared MBZ NS exhibited the smallest particle size (362.6 ± 12.3 nm) with unimodal particle size distribution and excellent short-term stability. DSC and FT-IR studies confirmed the crystallinity and the absence of interactions with the stabilizers used. The developed MBZ NS demonstrated ∼20 folds higher dissolution than MBZ alone in colonic pH. Cell experiments showed that HPMC E5 and SLS were safe on HT-29 and HT-116 cell lines. In addition, IC50 of MBZ-NS was found to be 1.028 ± 0.030 μM and 0.884 ± 0.050 μM in HT-29 and HT-116 cell lines, respectively. Furthermore, 1.5 folds and 1.8 folds reduction in 3D tumor spheroids after treatment with MBZ-NS was observed compared to the control and MBZ physical mixture. From the In Vitro Live/Dead Cell Assay higher amount of red fluorescence in treatment groups confirmed a large number of dead cells compared to the control. In a nutshell, the produced MBZ NS could be employed as a promising formulation to achieve a higher dissolution rate and anticancer efficacy against colorectal cancer of repurposing drug MBZ.

Development and Evaluation of Solid Dispersion-Based Sublingual Films of Nisoldipine.

Nisoldipine (NIS) is a calcium channel blocker that exhibits poor bioavailability (~5%) due to low aqueous solubility and presystemic metabolism in the gut wall. In this context, the present work aimed to develop NIS solid dispersion (NISSD)-based sublingual films using solvent casting technique to improve the dissolution. Phase solubility studies indicated that Soluplus® was the most effective carrier for improving the aqueous solubility of NIS. NISSDs were initially developed using the solvent evaporation method. Fourier transform infrared spectrometric studies were found to display the characteristic vibrational bands related to C=O stretching and N-H deformation in NISSDs, proving the chemical integrity of the drug in NISSDs. Subsequently, bioadhesive sublingual films of NISSDs were formulated using solvent casting method, using hydroxypropyl methyl cellulose (HPMC) E5, E15, and hydroxy ethyl cellulose (HEC EF) as hydrophilic polymers and polyethylene glycol 400 (PEG 400) as plasticizer. The incorporation of NISSDs was found to produce clear films that displayed uniform content. The sublingual film of NISSDs composed of HPMC E5 (2% w/v), was found to display the least thickness (0.29 ± 0.02 mm), the highest folding endurance (168.66 ± 4.50 times), and good bioadhesion strength (12.73 ± 0.503 g/cm2). This film was found to rapidly disintegrate (28.66 ± 3.05 sec) and display near-complete drug release (94.24 ± 1.22) in 30 min. Incorporating NISSDs into rapidly bioadhesive sublingual films considerably improves drug dissolution. Overall, these research outcomes underscored the potential of rapidly dissolving bioadhesive sublingual films to evade gut metabolism and resolve the bioavailability issues associated with oral administration of NIS.

Nano-suspension loaded mucoadhesive mouth dissolving film of meclizine hydrochloride

Meclizine Hydrochloride belongs to class H1 antagonist, antiemetic and anti-vertigo in nature, it is a Biopharmaceutical classification system (BCS) class II drug and is practically insoluble in water. The bottom-up approach was used in the formulation of nanosuspension in which methanol and millipore water was used as solvent and anti-solvent respectively, the stabilizers used for preparation were Polyvinylpyrrolidone K30 (PVP K30) and Hydroxypropyl Methylcellulose E15 (HPMC E15) which were found to be compatible with the formulation after Fourier Transform Infrared (FTIR) and Differential scanning calorimeter (DSC) studies. Mouth dissolving films were formulated by solvent casting method using glycerine lubricated petri dish and were kept for heating in a hot air oven at 45°C overnight. Characterization of nanosuspension-loaded mucoadhesive mouth dissolving films was done by evaluating various characteristics, the highest drug content was found to be 92.43±0.49% in Mouth dissolving film (MDF) 2. In-vitro drug release studies indicate that nanosuspension-loaded mucoadhesive mouth-dissolving film has a rapid drug release rate as compared to plain drug-loaded mouth-dissolving films and marketed tablet formulation.

Development of the composition and technology of an orodispersible film with melatonin and magnesium citrate

sleep disorders are one of the most common problems among the population today. Numerous scientific publications indicate the effectiveness and safety of melatonin and magnesium use as active ingredients in medicinal products in older adults with sleep disorders. The technological development of an oromucosal preparation – an orodispersible film with melatonin and magnesium citrate is relevant in view of the possibility of increasing the patients’ compliance, those who find it difficult to take oral dosage forms (tablets, capsules) due to possible hand tremors and swallowing disorders. The aim of the study was to develop orodispersible films’ with melatonin and magnesium citrate formulations of various compositions, to conduct a comparative study of their technological parameters in order to select the optimal composition of excipients. The orodispersible films were made by solvent casting method. Melatonin and magnesium citrate were combined with representatives of 6 excipients groups (hydrophilic polymers: agar-agar, xanthan gum, sodium alginate, carboxymethyl cellulose, hydroxypropyl methyl cellulose E3, plasticisers: macrogol 400, glycerol and propylene glycol, saliva stimulants: ascorbic, lactic and citric acids, disintegrant: sodium croscarmellose, sweeteners: sorbitol, erythrol and sucralose, solvent: purified water). Formulations of 9 experimental samples were formed. The prepared solutions were filled into appropriate Petri dishes and dried in several steps. The technological parameters of the dried and cut into 2×3.5 cm orodispersible films were determined: appearance and surface characteristics, average weight and it`s uniformity, area and film thickness, folding endurance, in-vitro disintegration time, and physico-chemical parameter: surface pH value. Formulation No. 5, when dried at 60 ⁰C for 3 hours and 60 ⁰C for 3 hours / 40 ⁰C for 2 hours, and left for congealing for 24 hours at 25±2 ⁰C, formed dry to the touch, durable elastic transparent orodispersible film with very close stable values of parameters (average weight 0.40±0.01 g, area 7 cm2, thickness 0.32±0.05 mm and 0.32±0.03 mm, respectively, folding endurance ˃ 300, pH 6.70±0.04 and 6.74±0.05, respectively, in-vitro disintegration time 32.00±0.67 s and 31.00±0.67 s, respectively). The technology is suitable and it is possible to obtain dry to the touch, durable, elastic transparent films with satisfactory values of the studied parameters under the specified drying conditions.

IMPLEMENTING CENTRAL COMPOSITE DESIGN FOR THE DEVELOPMENT OF TACROLIMUS FILM FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to develop fast-dissolving films (FDFs) of the immunosuppressant drug tacrolimus monohydrate for sublingual administration, employing central composite design (CCD), to improve its bioavailability. Methods: Tacrolimus: β-cyclodextrin inclusion complexes prepared earlier were formulated into FDFs. CCD was used for developing optimal film formulation with the desired characteristics. The solvent casting method was used for the preparation of films. For optimization, the independent variables selected were the concentration of hydroxy propyl methyl cellulose E5 (HPMC E5) (X1) and concentration of croscarmellose sodium (CCS) (X2) and the responses were disintegration time (Y1) and percentage drug release at 5 min (Y2). The suggested optimal films were subjected to further characterization. Results: All the formulations showed good mechanical properties. The composition of optimized FDF constituted 3.016% w/v of HPMC and 11.731%w/w of CCS and its average disintegration time was 27.28s and showed 83.13% mean drug release at 5 min. Differential Scanning calorimetry (DSC) analysis showed complete dispersion and partial conversion into the amorphous form of the drug, which was also confirmed by X-ray diffraction (XRD) studies. Scanning Electron Microscopy (SEM) revealed the smooth and porous nature of the film. Conclusion: The developed FDF may be used sublingually for delivering tacrolimus efficiently, avoiding its oral bioavailability problems.

Factors affecting on in vitro release of miconazole from in situ ocular gel.

The reason for conducting this study is to prolong release of miconazole in the ocular site of action by ocular-based gels (OBGs) formulations. The formulation factors affecting on the release from OBG should be studied using various gelling agents in various concentrations to achieve the improvement in retention and residence time in response to prolonged release. In this study, the formulations were prepared using carbopol 940, pectin, sodium alginate, poloxamer 407, and poly(methacrylic acid) at 0.5%, 1%, and 1.5% w/v, respectively. Hydroxypropyl methylcellulose E5 (HPMC E5) 1% was added as thickening agent/viscosity builder. The formulation containing carbopol 940, pectin and sodium alginate at 1.5% w/v, displayed a noticable improvement in viscosity, gelling capacity, and extended release for 7 h in comparison with the reference drug. Overall, the release showed that the sodium alginate with HPMC E5 form in situ gel which had longer time of release reach to 12 h compared with other polymers. the release of miconazole from the OBGs affected significantly by two factors includes gelling capacity and viscosity builder. The novelty of this study is supporting the delivery of ocular drugs through a cornea as an important key of the eye instead of dependence on an internal blood supply using an oral or a parental administration.

Fabrication of Hydroxypropyl Methylcellulose Orodispersible Film Loaded Mirtazapine Using a Syringe Extrusion 3D Printer

Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine.

The Development of Eletriptan Hydrobromide Immediate Release Buccal Films Using Central Composite Rotatable Design: An In Vivo and In Vitro Approach.

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 ± 1.13), while a maximum of 92.87 ± 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 µm. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t½) of 4.54 ± 0.18 h and a Cmax of 128 ± 0.87 (ng/mL); Tmax was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively.

Methylphenidate Fast Dissolving Films: Development, Optimization Using Simplex Centroid Design and In Vitro Characterization.

The focus of this study was to design and optimize methylphenidate hydrochloride mouth dissolving film (MDF) that can be beneficial in an acute condition of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Solvent casting method was used for the preparation of this film. Optimization of the effect of independent variables such as the number of polymers and active pharmaceutical ingredients [hydroxypropyl methyl cellulose (HPMC) E5, HPMC E15, and maltodextrin], % of drug release, disintegration time, and tensile strength of the film done using simplex centroid design. Complex formation of the film was tested using fourier-transform infrared spectroscopy and differential scanning calorimetry study. The multiple regression analysis was obtained from equations of the results that adequately describe influence of the independent variables on the selected responses. Polynomial regression analysis, contour plots, and 3-D surface plots were used to relate dependent and independent variables. Experimental results indicated that different polymer amounts had complex effects on % drug release from the film, disintegration time as well as the tensile strength of the film. The observed responses were in near alignment with expected values calculated from the developed regression equations as shown by percentage relative error. Final formulation showed more than 95% drug release within 2 min and was shown to disintegrate within a minute that had good tensile strength. These findings suggest that MDF containing methylphenidate hydrochloride is likely to become a choice of methylphenidate hydrochloride preparations for treatment in ADHD and narcolepsy conditions.

'Tablet-in-Syringe': A Novel Dosing Mechanism for Dysphagic Patients Containing Fast-Disintegrating Tablets Fabricated Using Semisolid Extrusion 3D Printing.

With the ability to fabricate personalized dosage forms and considerably shorter manufacturing time, semisolid extrusion (SSE) 3D printing has rapidly grown in popularity in recent years as a novel, versatile manufacturing method that powers a wide range of applications in the pharmaceutical field. In this work, the feasibility of using SSE 3D printing to fabricate fast-disintegrating tablets (FDTs) that are pre-filled in dosing syringes was evaluated. The novel design approach, ‘tablet-in-syringe’, was aimed to ease the oral drug administration and improve the dosing accuracy for dysphagic patients. The effect of varying polymer (hydroxypropyl methylcellulose E15) concentrations and printing parameters (e.g., extrusion rate) on dimensional accuracy, physicochemical properties, disintegration time, and content uniformity of 3D-printed FDTs was studied. An overall comparison of results demonstrated that the best FDT formulation among those developed was with a polymer:drug ratio (w/w) of 1:30, printed at extrusion rate of 3.5 μL/s. The diameter of printed filaments of this formulation was observed to be similar to the nozzle diameter (22G), proving that good printing accuracy was achieved. This FDTs also had the fastest disintegration time (0.81 ± 0.14 min) and a drug (phenytoin sodium, as the model drug) content uniformity that met pharmacopeial specifications. Although the flow characteristics of the dissolved formulation still need improvement, our findings suggested that the novel ‘tablet-in-syringe’ could potentially be considered as a promising fast-disintegrating drug delivery system that can be personalized and manufactured at—or close to—the point of care for dysphagic patients using SSE.

The effect of binder types on the breakage and drying behavior of granules in a semi-continuous fluid bed dryer after twin screw wet granulation

Current study investigated the effect of different binder types on the granule drying process and the granule breakage behavior in a semi-continuous fluid bed dryer integrated in the C25 ConsiGma-system. The studied binders (i.e. hydroxypropyl pea starch, hydroxypropyl methylcellulose E15, polyvinylpyrrolidone K12, and starch octenyl succinate CO 01) required different liquid amounts to produce similar granule quality. These different liquid requirements were translated into different drying conditions for each binder to result in sufficiently dry granules at the end of a drying cycle. By comparing the size distribution of the granules before entering and after exiting the fluid bed dryer, granule breakage could be evaluated. No effect of the binder type on the granule breakage during drying was observed. However, differences in granule breakage were observed for the binders when processed with the horizontal set-up of the C25 system, as granule breakage during pneumatic transport depended on the binder type. Only one binder (hydroxypropyl pea starch) allowed to avoid granule breakage during the entire process. Furthermore, this research showed that the drying process was mainly steered by the liquid requirements for granulation, and that these liquid requirements depended on the binder used.

Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Neoteric Approach of Fluoxetine Laden Orodispersible Film for Non-compliant Pediatric Patients of Selective Mutism and Obsessive-compulsive Disorder.

The objective of this research was to fabricate, characterize, and optimize fluoxetine laden orodispersible film (ODF), in enhancing dosage forms options for the pediatric population suffering from incapacitating psychotic disorders of selective mutism and obsessive-compulsive disorder, which will be ultimately beneficial in enhancing compliance factor and the quality of pharmacotherapy. Solvent casting technique was used to formulate the ODF formed by natural hydrophilic polymers matrix of hydroxypropyl methylcellulose E15 and pullulan. Propylene glycol as plasticizing agent imparted satisfactory tenacity and flexibility to ODFs. Fourier transform infrared spectroscopy studies were performed to investigate any potential compatibility, and the results revealed no potential interaction between fluoxetine and excipients. Developed ODFs were evaluated for physicochemical properties, content uniformity, in vitro disintegration time, and in vitro dissolution time studies. Results: The experimental data. The experimental data suggested that different polymer concentrations had a complex effect on content uniformity, in vitro disintegration time, and cumulative percentage drug release from the ODFs. TF7 was the most optimized formulation with a disintegration time of 10.66 sec and 99.37% drug release within 3 min. Additionally, the most optimized fluoxetine ODF was submitted to a Universal Testing Machine for tensile strength and percentage elongation determination. It was also further evaluated by thermogravimetric analysis, scanning electron microscopy and X-ray diffraction. Fluoxetine ODFs of good pharmaceutical quality can be prepared on a small scale. Therefore, the perspective of using fluoxetine ODFs for individualized pharmacotherapy to ameliorate the compliance issues in selective mutism and OCD pediatric patients can be considered.

The impacts of method selectivity and binders on the properties of carbamazepine granules and their applications: A case study

Background: Carbamazepine (CBZ) is a BCS II class drug, having many challenges in solubility, flowability, and compactibility. The study focused on the improvement of solubility, flow behavior, and drug release of carbamazepine. Methods: Low shear granulation (LSG), extrusion spheronization (ES), high shear granulation (HSG), fluid bed granulation (FBG), and hot melt granulation (HMG) methods were employed to prepare CBZ granules. Polyvinylpyrrolidone (PVP) K29/32, PVP K90, and Hydroxypropyl methylcellulose (HPMC) E5 were used as a binder. The drug to binder ratio was maintained in the proportion of 95:5. The nature of granules was analyzed by using X-ray Diffraction and Differential Scanning Calorimetry techniques. A powder flow tester was utilized to study the flow characteristics of the granules. Results: The HMG has successfully converted the crystalline structure of CBZ granules into an amorphous form. Dispersive and distributive mixing in the HMG has achieved better solid dispersion and fast drug release. The ES technique has reported the incompressible nature of the granules. PVP K90 and HPMC E5 were superior binders for imparting strength to the CBZ granules than PVP K29/32. The FBG has exhibited the free-flowing nature of granules due to their uniform and spherical shape. Conclusion: The HMG and FBG were the most effective methods that have remarkably improved drug release, flow properties, and compactibility of CBZ granules.