Dispersion Formulation Research Articles

Preparation and Characterization of Carvedilol Solid Dispersion by Kneading Method

Solid dispersion using hydrophilic carrier is one of the approaches that has a potential to increase solubility, dissolution rate and consequently the oral bioavailability of poorly-water soluble drugs. In this study, class II drug "Carvedilol" (CVD) was used because of its poor solubility, it serves as a model drug that contributes to irregular dissolution and limited bioavailability. CVD: PVP K30 solid dispersion formulations SD1, SD2 and SD3 were prepared by kneading method at different weight ratios ,1:1; 1:2 and 1:4 respectively and evaluated for drug content, solubility and dissolution rate. Kneading method enhances the stability of drugs and suitable for processing thermolabile substances. The optimum solid dispersion ratio was characterized also for drug-carrier interaction by FTIR spectroscopy, and crystallinity by SEM and PXRD and compared with physical mixture and pure drug powder.
 The results showed that the solubility of carvedilol increased by increasing the proportion of PVP K30 used in the dispersion of the drug. On the other hand, dissolution study revealed a significant enhancement in the dissolution rate of the drug using solid dispersion compared to pure drug and physical mixture. X-ray diffraction of the solid dispersion suggest that the drug's transformation from crystalline to amorphous form may be responsible for the observed improvement in dissolving rate. The carvedilol solid dispersion improved the solubility and dissolution, which depend on the carrier concentration ratio. The dissolution of drugs increased with an increase in carrier content. The studies of PXRD, SEM, and FTIR revealed the amorphous nature of the drug in solid dispersion. The solid dispersion by kneading approach using PVP K30 as a carrier is a potential method for improving CVD's solubility and dissolution rate.

Febuxostat solubilization and stabilization approach using solid dispersion method: Synergistic effect of dicalcium phosphate dehydrate and chitosan

Drug solubilization studies are continuously being conducted. Febuxostat (FBX) has a low solubility in water. This study aims to develop a stable FBX-solid dispersion (SD) formulation using a solvent evaporation method. The solubilization strategy of FBX is to develope an optimal FBX-SD formulation by selecting a solubilizer and carrier through the screening method. The final selected solubilizer, macrogol 15 hydroxystearate and polyoxyl 15 hydroxystearate (Kolliphor® HS-15), is widely used in the pharmaceutical industry as a nonionic solubilizing and emulsifying agent and has low toxicity. Especially when commonly used in developing lipophilic drug formulations, it dissolves well in water and ethyl alcohol. The optimal composition ratio of the formulation (SD4) was FBX:HS-15®:granular dicalcium phosphate dehydrate (DCP-D): A synthetic magnesium aluminometasilicate (Neusilin®UFL2):chitosan = 1:3:3:1:1 (w/w) and showed 3.0-, 2.3-, and 1.1-fold higher dissolution (%) of FBX compared to that of the Feburic tab® in pH 1.2 media, distilled water (DW), and pH 6.8 buffer, respectively. Also, in vitro release and in vitro permeability in SD4 formulation showed higher than that of Feburic tab®. Based on its stability over 6 months, it was confirmed that chitosan acted as a stabilizer. Moreover, due to weak intermolecular interactions, FBX in the SD4 formulation was considered to exist in a mixed state of amorphous and crystalline FBX. In conclusion, the improved dissolution (%) and stability of FBX in SD4 formulation were secured through the synergistic effect of excipients.

Formulation and Characterization of Matrine Oil Dispersion to Improve Droplet Wetting and Deposition.

The unreasonable use of chemical pesticides has caused serious damage to crops and the ecological environment. The botanical pesticide matrine has attracted attention as an environmentally friendly pesticide. Compared with traditional spraying methods, unmanned aerial vehicle (UAV) spraying has the advantages of safety, rapidity, uniform droplets, low dosages, and no terrain or crop restrictions. In this study, matrine OD was prepared according to the application requirements of flight prevention preparations using three different emulsifiers. The stability, wettability, particle size and distribution, and spraying performance of matrine OD were studied. The results indicated that when the amount of emulsifier was 8%, the three types of matrine OD had good stability. The stability, wettability, particle size and distribution, and spray performance of the suspension prepared using emulsifier VO/03 were better than the other two emulsifiers. Therefore, matrine OD prepared using 8% VO/03 could be used for ultra-low-volume sprays and aerial applications. In this study, we provide a theoretical basis and technical guidance to develop pesticide formulations for aerial applications.

Does Media Choice Matter When Evaluating the Performance of Hydroxypropyl Methylcellulose Acetate Succinate-Based Amorphous Solid Dispersions?

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is a weakly acidic polymer that is widely used in the formulation of amorphous solid dispersions (ASDs). While the pH-dependent solubility of HPMCAS is widely recognized, the role of other solution properties, including buffer capacity, is less well understood in the context of ASD dissolution. The goal of this study was to elucidate the rate-limiting steps for drug and HPMCAS release from ASDs formulated with two poorly water soluble model drugs, indomethacin and indomethacin methyl ester. The surface area normalized release rate of the drug and/or polymer in a variety of media was determined. The HPMCAS gel layer apparent pH was determined by incorporating pH sensitive dyes into the polymer matrix. Water uptake extent and rate into the ASDs were measured gravimetrically. For neat HPMCAS, the rate-limiting step for polymer dissolution was observed to be the polymer solubility at the polymer-solution interface. This, in turn, was impacted by the gel layer pH which was found to be substantially lower than the bulk solution pH, varying with medium buffer capacity. For the ASDs, the HPMCAS release rate was found to control the drug release rate. However, both drugs reduced the polymer release rate with indomethacin methyl ester having a larger impact. In low buffer capacity media, the presence of the drug had less impact on release rates when compared to observations in higher strength buffers, suggesting changes in the rate-limiting steps for HPMCAS dissolution. The observations made in this study can contribute to the fundamental understanding of acidic polymer dissolution in the presence and absence of a molecularly dispersed lipophilic drug and will help aid in the design of more in vivo relevant release testing experiments.

The Amorphous Solid Dispersion of Chrysin in Plasdone® S630 Demonstrates Improved Oral Bioavailability and Antihyperlipidemic Performance in Rats.

Chrysin is a flavonoid with various biological activities. However, its low water solubility and strong metabolism render its oral bioavailability rather poor. This study aimed to develop a stable solid dispersion formulation of chrysin to improve the dissolution of chrysin, so as to increase its oral bioavailability and improve its antihyperlipidemic activities. A solid dispersion of chrysin was prepared using a solvent evaporation method, with Plasdone® S630 as the hydrophilic carrier. The formulations were characterized via X-ray diffraction, in vitro dissolution studies, and stability studies. An in-situ perfusion model was used to evaluate the absorption rates. Plasma pharmacokinetics and antihyperlipidemic performance after the oral administration of the chrysin formulations were investigated in rats. It was found that the solid dispersion of chrysin prepared using the drug-polymer mass ratio of 1:6 can form the optimized formulation. X-ray diffraction results showed that the chrysin was in an amorphous state in this optimized formulation. The cumulative release percentage of the optimized solid dispersion of chrysin at pH 1.2 and pH 6.8 was elevated to above 90% within 24 h, indicating that the formulation could enhance the dissolution rates of chrysin. Stability studies showed that the optimized formulation presented acceptable long-term storage stability, but it was susceptible to high temperature and humidity. The solid dispersion of chrysin showed higher absorption rates in the in-situ perfusion model. Pharmacokinetic studies revealed that Cmax and AUC after the intragastric administration of solid dispersion of chrysin were appreciably higher than those resulting from chrysin suspension. The oral bioavailability of the solid dispersion of chrysin was 41 times higher than that of chrysin suspension. Pharmacological studies suggested that the solid dispersion of chrysin was more powerful than chrysin raw material in improving biochemical indicators in the hyperlipidemic model in rats. This study reveals the potential use of a novel oral formulation of chrysin to reduce the currently required high dose.

A Comparative Study on Cyclodextrin Derivatives in Improving Oral Bioavailability of Etoricoxib as a Model Drug: Formulation and Evaluation of Solid Dispersion-Based Fast-Dissolving Tablets.

Etoricoxib, as a model drug, has a poor solubility and dissolution rate. Cyclodextrin derivatives can be used to solve such a problem. A comparative study was run on three cyclodextrin derivatives, namely β-CD, HP β-CD, and SBE β-CD, to solve the drug problem through the formulation of solid dispersions and their preparation into fast-dissolving tablets. Preparations utilized different (1:1, 1:2, and 1:4) drug:carrier ratios. Nine fast-dissolving tablets (containing 1:4 drug: carrier) were formulated using Prosolv ODT® and/or F-melt® type C as super-disintegrants. Optimized formulation was chosen based on a 32 factorial design. The responses chosen were the outcomes of the in vitro evaluation tests. The optimized formulation that had the highest desirability (0.86) was found to be SD-HP3, which was prepared from etoricoxib: HP β-CD at a 1:4 ratio using equal amounts of Prosolv ODT® and F-melt® type C. An in vivo evaluation of SD-HP3 on a rabbit model revealed its superiority over the marketed product Arcoxia®. SD-HP3 showed a significantly lower Tmax (13.3 min) and a significantly higher Cmax (9122.156 μg/mL), as well as a significantly higher AUC, than Arcoxia®. Thus, the solubility, dissolution, and bioavailability of etoricoxib were significantly enhanced.

Determinants of Antituberculosis Drug Acceptability among Children with Tuberculosis in Osun State Nigeria

Acceptability of antituberculosis drugs by affected caregivers and children is key to disease elimination. This is affected by many factors including drug, patients, and health institution-related factors. This study aims to assess the influence of the introduction of dispersible formulation on acceptability of antituberculosis drugs. A historical cohort design was used to assess and compare the acceptability of old loose non-dispersible and new dispersible antituberculosis drugs, using a convergent parallel mixed method of data collection. Determinants of tuberculosis drug acceptability were assessed using binary logistic regression. The findings were triangulated with results from the qualitative data. The rate of acceptability of the new dispersible formulation, 112 (88.2%) was significantly higher than the rate of acceptability of old loose non-dispersible drugs, 13 (10.5%), p<0.001. The median age of children with good acceptability, 7.0 (4.0 – 10.0) years was significantly lower than those with poor acceptability, 10.0 (8.0 – 13.0) years, p <0.001. Drug formulation was a significant predictor of acceptability; the fixed-dose dispersible drug had a higher probability of being acceptable relative to lose non-dispersible formulation, (Odd Ratio = 62.3, p <0.001, 95% CI= 25.3 – 153.3). The qualitative data showed that health education about tuberculosis has positive influences on drug acceptability. In conclusion, the formulation of drugs is a key factor in the acceptability of antituberculosis drugs. Hence, there is a need to further promote the recently introduced child-friendly antituberculosis drugs, coupled with strengthening the health education of caregivers to achieve tuberculosis elimination. Keywords: Antituberculosis, Acceptability, Fixed-Dose Combination, Dispersible, Tuberculosis.

Pharmacokinetics and optimized dosing of dispersible and non-dispersible levofloxacin formulations in young children.

Levofloxacin is used for treatment and prevention of rifampicin-resistant (RR)-TB in children. Recent data showed higher exposures with 100 mg dispersible compared with non-dispersible tablet formulations with potentially important dosing implications in children. We aimed to verify and better characterize this finding. We conducted a crossover pharmacokinetic trial in children aged ≤5 years receiving levofloxacin RR-TB preventive therapy. Pharmacokinetic sampling was done after 15-20 mg/kg doses of levofloxacin with 100 mg dispersible and crushed 250 mg non-dispersible levofloxacin formulations. A population pharmacokinetic model was developed. Twenty-five children were included, median (IQR) weight and age 12.2 (10.7-15.0) kg and 2.56 (1.58-4.03) years, respectively. A two-compartment model with first-order elimination and transit compartment absorption best described levofloxacin pharmacokinetics. Allometric scaling adjusted for body size, and maturation of clearance with age was characterized. Typical clearance in a 12 kg child was estimated at 4.17 L/h. Non-dispersible tablets had 21.5% reduced bioavailability compared with the dispersible formulation, with no significant differences in other absorption parameters.Dosing simulations showed that current recommended dosing for both formulations result in median exposures below adult-equivalent exposures at a 750 mg daily dose, mainly in children >6 months. Higher levofloxacin doses of 16-30 mg/kg for dispersible and 20-38 mg/kg for crushed non-dispersible tablets may be required in children >6 months. The dispersible paediatric levofloxacin formulation has improved bioavailability compared with the crushed non-dispersible adult formulation, but exposures remain below those in adults. We propose optimized age- and weight-based dosing for levofloxacin, which require further evaluation.

New waterborne polyurethane/silica hybrid dispersions based on natural rubber and prepared by sol-gel process: Effects of amino alkoxy-silane and nano-silica contents on dispersion stability and films properties

A bio-polyol based issued from natural rubber was successfully synthesized for the preparation of waterborne polyurethane (WPU) and hybrid waterborne polyurethane (HWPU). The WPU was prepared by prepolymer process from hydroxyl telechelic natural rubber (HTNR), using dimethylolpropionic acid (DMPA) and hexamethylene diisocyanate (HDI). A series of new HWPUs was successfully synthesized by the sol-gel process, using 3-aminopropyltriethoxysilane (APTES) as a coupling agent. Effects of the amount of APTES (0.8–1.3%wt) on properties of the HWPU were investigated. The WPU and HWPU with APTES content ranging from 0.8 to 1.0%wt showed well-dispersed particles with a long shelf life exceeding 3 months. The particle size increased with APTES content. In addition, the HWPUs showed increasing zeta potential with APTES content. The morphology and shape of particles were observed from Transmission Electron Microscopy (TEM) imaging. The chemical structures in WPU and the series of HWPUs were confirmed by FT-IR. The tensile strength of HWPU was improved on incorporating Si–O–Si linkages into the WPU backbone through a sol-gel process. Moreover, effects of the amount of nano-silica (0–15%wt) on properties of the HWPU/silica were investigated. TEM images demonstrated miscibility and specific interactions between HWPU and the dispersed nano-silica particles. The morphology of HWPU/silica films was characterized by Scanning electron Microscopy (SEM), and the elemental analysis of surfaces was carried out by Energy Dispersive X-ray Spectroscopy (EDX). Additionally, nano-silica content enabled the hydrophobicity of HWPU/silica films, leading to water repellence and good water resistance. Moreover, the mechanical and thermal properties were significantly improved on increasing nano-silica content. The investigation demonstrated that using HTNR polyol in the formulation of a new HWPU dispersion is an environmentally friendly alternative, in which performance of the film is improved on adding nano-silica via a sol-gel process. The novel films have potential for coating applications.

Self-micellizing solid dispersion of tacrolimus: Physicochemical and pharmacokinetic characterization.

The present study was undertaken to develop a self-micellizing solid dispersion (SMSD) of tacrolimus (TAC) to improve the biopharmaceutical properties of TAC. An SMSD formulation of TAC (SMSD/TAC) and amorphous solid dispersion formulation of TAC (ASD/TAC) were prepared with Soluplus® , an amphiphilic copolymer, and hydroxypropyl cellulose, respectively. Physicochemical properties were characterized in terms of morphology, crystallinity, storage stability, interaction of TAC with Soluplus® , and micelle-forming potency; pharmacokinetic behavior was also evaluated in rats. Tacrolimus in both formulations was in an amorphous state. After storage at 40°C/75% relativity humidity for 4weeks, there were no significant changes in the crystallinity of TAC between nonaged and aged SMSD/TAC, whereas slight recrystallization was observed in aged ASD/TAC. The results of circular dichroism (CD) and infrared spectroscopic analyses were indicative of the potent drug-polymer interaction in SMSD/TAC, possibly leading to the prevention of recrystallization. Compared with other TAC samples, SMSD/TAC exhibited significant improvement in the dissolution behavior of TAC through the immediate formation of fine micelles. After the oral administration of TAC samples (10mg TAC/kg) to rats, there was marked enhancement in systemic exposure to TAC with both formulations; in particular, SMSD/TAC achieved an increase in bioavailability ca. 20-fold higher than crystalline TAC. The SMSD approach might provide an effective dosage form for TAC with enhanced physicochemical stability and oral absorption.

Despite warnings, co-medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but XS004, a novel oral dasatinib formulation, provides reduced pH-dependence, minimizing undesirable drug-drug interactions.

Dasatinib and other tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, as a lipophilic weak base, crystalline monohydrate, dasatinib (Sprycel®) is poorly soluble, rendering a pH-dependent absorption and a highly variable bioavailability. Thus, co-medication with proton pump inhibitors (PPI) profoundly impairs dasatinib uptake and is clearly recommended against. XS004 is a novel oral immediate release and amorphous solid dispersion (ASD) formulation of dasatinib and is bioequivalent to the original crystalline dasatinib at 30% lower dosages. XS004 is designed to mitigate gastric pH dependency, thus optimizing absorption and bioavailability. We investigated the prevalence of dasatinib and PPI co-medication among chronic-phase CML patients in a real-world setting and assessed the plasma pharmacokinetics (PK) of XS004 with and without PPI co-medication (omeprazole) in healthy volunteers. Using the Swedish CML and Prescribed Drug Registers, we identified 676 TKI-treated CML patients; 320 (47%) had been prescribed PPI at some point after CML diagnosis. Among dasatinib-treated patients, the 2-year cumulative PPI co-medication was 24%. Interestingly, the 5-year overall survival was significantly lower for TKI-treated CML patients with versus without PPI co-medication (79% vs. 94%; hazard ratio 3.5; 95% confidence interval, 2.1-5.3; p < .0001). When assessing PK of XS004, neither Cmax nor area under the plasma concentration curve levels in plasma were significantly altered by the PPI co-medication. In conclusion, despite warnings, PPI co-medication is common among dasatinib-treated CML patients in a real-world setting. The new XS004 ASD formulation of dasatinib provided, in contrast to original crystalline dasatinib, superior pH independence with stable bioavailability, thereby minimizing drug-drug interactions. This may improve the long-term efficacy and tolerability of dasatinib in CML.

Pharmacokinetic and Bioequivalence Evaluation of Two Cefprozil Dispersible Tablets in Healthy Chinese Volunteers.

This study aimed to assess the bioequivalence of 2 cefprozil dispersible tablet formulations (250mg) in healthy Chinese volunteers under fasting and fed conditions and to determine the pharmacokinetics of cefprozil. A randomized, single-dose, open-label, 2-formulation, 2-period study was conducted. The elimination period for this study was 7 days. Forty-eight healthy volunteers received 250-mg cefprozil dispersible tablets in each study period under both test and reference conditions. The test and the reference cefprozil were bioequivalent in healthy Chinese volunteers, and there was no significant food effect in individuals receiving either formulation. No serious adverse event was recorded, and no volunteers withdrew from the study.

Effect of process parameters in high shear granulation on characteristics of a novel co-processed mesoporous silica material

In this study, insights into the development and optimization of a co-processed excipient based on mesoporous silica are presented. The main advantage of such a material is that it is appropriate for direct tablet compression and has a sufficiently large specific surface area to be suitable for potential subsequent drug loading and formulation of (amorphous) solid dispersions. Our aim was to use a Design of Experiments approach to investigate which process parameters in high shear granulation affect the characteristics of such a co-processed material. The parameters included were the amount of binder (isomalt), the amount of water (granulation liquid), the water addition rate and the speed of the impeller. The responses evaluated and modelled were particle size and its distribution, specific surface area, bulk density, flowability, compressibility and compactibility. The models obtained showed good quality in terms of goodness of fit and predictive power. Active effects were identified for all responses, giving a thorough insight into factors affecting the material characteristics. Optimization experiments resulted in products with the desired characteristics (high specific surface area, large particle size, good flow and compression properties) and confirmed the validity of the generated models.

Solid amorphous formulations for enhancing solubility and inhibiting Erlotinib crystallization during gastric-to-intestinal transfer

The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL.

DESIGN, OPTIMIZATION, AND CHARACTERIZATION OF A NOVEL AMORPHOUS SOLID DISPERSION FORMULATION FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF TICAGRELOR

Objective: The study aims to enhance the solubility and dissolution of ticagrelor by formulating an amorphous solid dispersion using the hot melt extrusion technique. Methods: Solubility of ticagrelor is very limited in water and buffers of pH 1.2 to 6.8, which is one of the prime reasons for its low oral bioavailability. Amorphous solid dispersions were prepared using the Hot Melt Extrusion technique using different polymers, plasticizers, and surfactants. The formulation is optimized based on the level of polymer in the formulation. The final formulation of Ticagrelor Amorphous Solid Dispersion is made with a drug-polymer ratio of 1:3, keeping the plasticizer level at 10% of the polymer along with a surfactant Sodium Lauryl Sulfate. Results: The formulation showed an increase in solubility of 193.95-times in water, 50.71-times in 0.1 N HCl, 332.74-times in pH 4.5 acetate buffer, and 85.20-times in pH 6.8 phosphate buffer as compared to the pure drug. The drug release of the final formulation was found to be 70.0±4.4%, 55.4±1.1%, 35.5±2.1%, and 30.0±0.8% at 90 min, while the reference product showed a release of 9.4±1.1%, 20.7±0.5%, 8.4±0.3%, and 7.8±0.2% at 90 min in water, 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 Phosphate Buffer respectively. The drug release of the final formulation was found to be 99.1±3.8% at 60 min in 0.2% w/v Polysorbate-80 in water. Conclusion: In the present study, the amorphous solid dispersion of the poorly-soluble drug ticagrelor was successfully prepared. The polymer, Plasdone S630, is considered the most suitable with ticagrelor for formulating amorphous solid dispersion using Hot Melt Extrusion technology to increase the solubility and dissolution of the drug.

INCREASING SOLUTION IN THE DRUG SIMVASTATIN WITH SOLID DISPERSION TECHNIQUE USING POLYMER SOLUPLUS

Objective: Simvastatin is a bioactive compound belonging to the class II Biopharmaceutic Classification System (BSC), which has high permeability but low solubility. The low solubility of Simvastatin showed by low bioavailability so modification is required for its solubility. Methods: There are many techniques to improve the solubility of poorly water-soluble drug; one of them is solid dispersion prepared by the solvent evaporation method. This study aims to determine the solid dispersion formulation of simvastatin using soluplus as a polymer with a ratio of 1:1, 1:2, 1:3, and 1:4 which is employed to increase the solubility and dissolution rate of simvastatin. Furthermore, characterization was carried out using IR spectrophotometry, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Results: The maximum solubility test yielded a 1:4 solid dispersion, which is up to 20 times more potent than pure simvastatin. Simvastatin's solubility increased from 17.33% to 82.50% for a 1:4 solid dispersion at 60 min, affecting the dissolution rate as well. Conclusion: A solid dispersion was formed in an amorphous state, as evidenced by the fact that the results of characterization using IR spectrophotometry showed no new functional groups were formed in the solid dispersion, the results of characterization using Differential Scanning Calorimetry (DSC) showed a decrease in melting point, and the results of x-ray diffraction characteristics did not show a sharp peak.

Design and characterization of dual‐pronged liposome‐embedded gel for enhanced dermal delivery

AbstractThe present study aims to develop a combination of Nigella sativa seed oil (NSO) and virgin coconut oil (VCO)‐loaded liposomal gel as a topical drug delivery system for vitiligo. A 3 × 3 factorial design approach was adopted to study the effect of variables on liposome characteristics and performance. A total of nine batches were formed. The cholesterol: phospholipid (wt/wt) and drug (NSO:VCO) ratios (vol/vol) were marked as two independent variables, X1 and X2. The dependent variables selected were entrapment efficiency, vesicle size, and polydispersity index. Liposomes were fabricated by thin‐film hydration technology. A carbopol gel matrix was used to embed the optimized liposome vesicles, which were then tested for pH, viscosity, ability to spread, and stability. Better stability for topical drug delivery systems was demonstrated by the incorporation of liposomes in gel prepared from cross‐linked polyacrylate. In vitro drug release, ex vivo drug permeation and drug retention were compared between liposomal and conventional preparations. Skin permeation and skin retention studies demonstrated that the prepared liposomal gel significantly extended the penetration of drugs into the skin and retained more drugs in the skin when compared to liposomal dispersion and conventional gel formulations. The stability of the developed liposomal gel was assured at 5 ± 3°C and 25 ± 2°C. From the studies described above, it is concluded that liposomal gel is the best‐suited formulation among all the preparations examined. The enhanced epidermal localization and accumulation of therapeutic moiety on the disease site could improve the effectiveness of the treatment.

Can Pure Predictions of Activity Coefficients from PC-SAFT Assist Drug-Polymer Compatibility Screening?

The bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved via the formulation of an amorphous solid dispersion (ASD), where the API is incorporated into a suitable polymeric carrier. Optimal carriers that exhibit good compatibility (i.e., solubility and miscibility) with given APIs are typically identified through experimental means, which are routinely labor- and cost-inefficient. Therefore, the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state, a popular thermodynamic model in pharmaceutical applications, is examined in terms of its performance regarding the computational pure prediction of API-polymer compatibility based on activity coefficients (API fusion properties were taken from experiments) without any binary interaction parameters fitted to API-polymer experimental data (that is, kij = 0 in all cases). This kind of prediction does not need any experimental binary information and has been underreported in the literature so far, as the routine modeling strategy used in the majority of the existing PC-SAFT applications to ASDs comprised the use of nonzero kij values. The predictive performance of PC-SAFT was systematically and thoroughly evaluated against reliable experimental data for almost 40 API-polymer combinations. We also examined the effect of different sets of PC-SAFT parameters for APIs on compatibility predictions. Quantitatively, the total average error calculated over all systems was approximately 50% in the weight fraction solubility of APIs in polymers, regardless of the specific API parametrization. The magnitude of the error for individual systems was found to vary significantly from one system to another. Interestingly, the poorest results were obtained for systems with self-associating polymers such as poly(vinyl alcohol). Such polymers can form intramolecular hydrogen bonds, which are not accounted for in the PC-SAFT variant routinely applied to ASDs (i.e., that used in this work). However, the qualitative ranking of polymers with respect to their compatibility with a given API was reasonably predicted in many cases. It was also predicted correctly that some polymers always have better compatibility with the APIs than others. Finally, possible future routes to improve the cost-performance ratio of PC-SAFT in terms of parametrization are discussed.

Formulation of Dispersible Ayurvedic Kadha Tablet for the Management of Cold and Cough

The term “Ayurveda” combines the Sanskrit words ayur (life) and veda (science or knowledge). It is one of the traditional medicinal systems, with an established history of many centuries. Indian herbs, which are widely used in the preparation of Ayurvedic medicines in the form of Kadha to control various respiratory disorders such as, cough, cold and flu. In a traditional Kadha (decoction) preparation, the entire process is done manually Such as boiling, filtering and mixing of medicinal herbs and the aim of this research work was to skip all such manually process. The oral route of drug administration is most extensively used due to the obvious ease of administration. Dispersible tablets are a vital tool in keeping our children and elderly population healthy. Their ease of use and accurate dosing allow higher patient compliance and more reliable therapeutic effects. Medicinal plants and parts as like Tulsi (Rama-Tulsi) (Ocimum Sanctum Linn, family Lamiaceae), Ginger (Zingiber officinale, family Zingiberaceae), Clove (Syzygium aromaticum, family myrtaceae) and Turmeric (Curcuma longa, family Zingiberaceae) were used as a model drug. Phytochemicals present in these herbs, which have significant potential to heal cold and cough. The phytochemicals present in these herbs possess significant anti-inflammatory property. In order to determine the most effective type and optimal amount of superdisintegrants for dispersible tablets different formulation were evaluated. Wet granulation and direct compression methods were tried to develop dispersible tablet. Due to higher moisture in the granules the wet granulation method was not carried out further in the study and direct compress method was selected. Prepared tablets were tested for Appearance, Weight variation, Thickness, Friability (%), Hardness (kg/cm2 ), Disintegration time and IR spectroscopic analysis and finally for six months of stability studies at room temperature, 30ºC/60% RH and at 45ºC/75% RH. Sodium Starch Glycolate was superior to the other disintegrants and the non-fractionated granulation gave adequate dispersion. The ideal concentration was 1.33 % Sodium Starch Glycolate was used for the dispersible tablets

A review on orodispersible drug delivery system

The future of drug delivery holds great promise for orally dispersible dose formulations, which make application simple since no water requirement as compared to conventional solid dosage forms which requires significant volumes of fluids for administration. The objective for development of ODF provides a substitute for pills, syrups, and tablets in treating vomiting as well as nausea, particularly in children. On the basis of transdermal patch delivery system, a novel oral films drug delivery has been introduced. Fast dissolving films disintegrates quickly when come in contact with salivary secretion in the oral mucosa and released the drug fast approximately within 3 mins. ODFs are of different types, like sustained or controlled release, oral patches and fast dissolving films. They can be manufactured using a variety of method including solvent and semi solid casting, hot melt and solid dispersion extrusion, spray drying and rolling. Among them solvent casting method is the most employed method. ODFs comprises of active ingredient, polymer, plasticizer and additives like surfactants, sweetening and coloring agents. ODFs preparation requires hydrophilic polymer which provides quick dissolution in the oral cavity. Hydrophilic polymer act as base for ODFs formulation as they impart mouth feel and mechanical properties of the ODFs also dependent of polymer type. Oral thin-film provide fast drug dissolution precise dosage in a portable, safe, and handy manner that doesn't required water or any special equipment. This review article comprises of different methods for ODFs preparations, ODFs ingredients, ODFs benefits and drawbacks and their packaging.