Solid Dispersion Technique Research Articles

Improving the Bioavailability of Curcumin in Curcuma heyneana by Preparing Solid Dispersion

Curcuma heyneana or Temu Giring contains curcumin which has anti-aging potential and is traditionally used as a body scrub. This potential comes from the active ingredient (curcumin) which can prevent premature aging with its activity as an antioxidant, inhibitor of the tyrosinase enzyme, and inhibitor of the collagenase enzyme. So, it can prevent hyperpigmentation and inhibit the breakdown of collagen which can have an impact on skin aging. Oral dosage forms for anti-aging are starting to be found on the market and becoming a trend because of their convenient use. However, it is known that curcumin as an active ingredient of Temugiring, has poor solubility and bioavailability. The bioavailability of curcumin is low when administered orally due to its low absorption and its stability which decreases significantly when the pH is above 7. This study is a literature review of national and international literature databases that aims to determine the potential for increasing the bioavailability of curcumin using solid dispersion techniques. The results obtained indicate that making Temu Giring extract tablets containing curcumin using the solid dispersion method can increase the bioavailability of curcumin by overcoming the poor solubility, permeability, absorption, and stability of curcumin. By designing the Temu Giring extract using a solid dispersion method, the curcumin can be completely dissolved and released into the stomach. Keywords: Curcuma heyneana, Temu Giring, anti-aging, tablet, curcuminoid, antioxidant, solid dispersion.

Effect of Polymer Type, Concentration and Formulation Technique on Mucoadhesive Strength and Swelling Index of Clarithromycin Tablets

Effect of Polymer Type, Concentration and Formulation Technique on Mucoadhesive Strength and Swelling Index of Clarithromycin Tablets

Toxicity of Clove Oil Nanoparticles against Diamondback Moth Plutella xylostella (L.)

Plutella xylostella, diamondback moth (DBM), has been one of the most challenging insects to control in the world to date. Environmentally friendly methods of control, such as the use of botanical insecticides, are available. A formulation that can sustain the main compound's level is required, which can be accomplished through soluble powder nanoformulation. The goal of this research was to test and evaluate the ability of clove oil nanoparticles produced from polyethylene glycol 6000 (PEG 6000) to control DBM utilizing a solid dispersion technique. Bioassay by leaf dip method in laboratory was used to test the lethal effect of clove oil nanoparticles (CO-NPs) on DBM. Clove oil nanoformulation was successful because it produced nanoparticles (179.98 nm in diameter) while maintaining high levels of the active component eugenol. Clove oil nanoparticles may increase clove oil's toxicity to DBM, seen from the LC50 value after 24 h of treatment. The LC50 values for clove oil nanoparticles after 24 and 48 h of treatment were 10.308 and 9.451%, respectively.

Formulation and Characterization of Solid Dispersion of Oxcarbazepine

The purpose of the current study was to use the solid dispersion approach to improve the solubility of the medication oxcarbazepine, which is only moderately water soluble. The antiepileptic medication oxcarbazepine is used to treat seizures. Due to its high permeability and low water solubility, it falls under BCS class II. To prevent issues of this nature, it was imperative to increase the solubility of oxcarbazepine in accordance with British Pharmacopoeia (BP) solubility criteria since pure oxcarbazepine falls under the category of being only very slightly soluble. Solid dispersion technique has been used to try and increase the solubility of pure oxcarbazepine. Oxcarbazepine is also extensively metabolized by the liver. Attempt has been made to formulate solid dispersions containing oxcarbazepine to improve its solubility and dissolution rate to avoid first pass metabolism; to avoid difficulty.

Review on Laboratory Scale Solid Dispersion Techniques

Review on Laboratory Scale Solid Dispersion Techniques

Formulation for Enhancement of Solubility and Dissolution Rate of Simvastatin using Solid Dispersion

Solid dispersion preliminary solubility analysis was carried out for the selection of the carrier and solid dispersion was prepared with Hydroxy Propyl Methyl Cellulose (HPMC) and Methyl Cellulose (MC). These solid dispersions were analyzed for the solubility and in-vitro dissolution profile solid dispersion of drug with polymer has shown enhanced solubility with improved dissolution rate. Further FTIR, X-Ray studies were carried out. The solubility and dissolution rate of Simvastatin, a drug used for the treatment of hyperlipidaemia. Simvastatin is a selective competitive inhibitor of HMG Co-A reductase. However its absolute bioavailability is 5%. To increase the solubility of drug solid dispersion was prepared. Solid dispersion prepared with polymer in 1:5 ratios shows the presence of amorphous form confirmed by the characterization study. The present investigations showed that solubility of Simvastatin Sodium was markedly increased by its solid dispersion using PVP K30 as carrier. The formulation SDF8 containing (1:8) shows highest dissolution rate. Hence the solid dispersion a way is useful technique in providing fastest onset of action of Simvastatin Sodium as well as enhanced dissolution rate. The study also shows that dissolution rate of Simvastatin can be enhanced to considerable extent by solid dispersion technique with Polymer.

Technique Development in Improving the Solubility of Poorly Water Soluble Drugs (BCS II and IV)

Orally active drugs are currently available on the market. API should have adequate solubility and permeability to enhance its therapeutic efficacy when administered orally and obtain optimum bioavailability. Almost 40% of New Chemical Entities had limited solubility or fell into BCS class II and IV. Our review aims to summarize and discuss the development of methods and characterization for increasing the solubility of poorly aqueous drugs from papers published in Google Scholar, NCBI, Science direct, Researchgate, and MDPI. We checked that the methods used such as solid dispersion, cocrystal formation, and coamorphous can increase the solubility of API which has an impact on increasing bioavailability. The successful formation of solid dispersions, cocrystals and coamorphs can be confirmed by the characterization of PXRD, DSC and SEM. In conclusion, drug solubility is an important aspect of pharmacological effects. Drugs with high solubility can provide fast solubility rates and high bioavailability, reducing the dose administered. Solid dispersion, cocrystals, and coamorphous techniques, have succeeded in increasing the solubility of BCS class II and IV drugs.

Preparation and Evaluation of Pioglitazone Tablet by Solid Dispersion Technique

Pioglitazone is an oral hypoglycemic drug, used for the treatment of type 2 diabetes. The main objectives of this study were to improve aqueous solubility of Pioglitazone by preparing its solid dispersion by fusion method using various carriers that will improve its absorption and subsequent bioavailability. The prepared tablets (TF1-TF5) were evaluated for various parameters i.e.shape and size, weight variation, hardness, friability, disintegration time, drug content etc. The prepared tablet passed all the tests.Finally, it can be concluded that solid dispersion of Pioglitazone may be prepared to improve its solubility and dissolution. This will lead to better absorption and hence improved bioavailability of the drug (Pioglitazone).

Enhancing Solubility and Dissolution Behavior of Finasteride Using Solid Dispersion Technique by Carrier Screening and the New Preparation Instrument

Enhancing Solubility and Dissolution Behavior of Finasteride Using Solid Dispersion Technique by Carrier Screening and the New Preparation Instrument

Comparative assessment of solubility enhancement of itroconazole by solid dispersion and co-crystallization technique: Investigation of simultaneous effect of media composition on drug dissolution

Solubility of the drug is an important property of the drug as it affects the release, absorption, dissolution rate and ultimately bioavailability of the drug. Hence, the poorly aqueous soluble drug, need to be processed, to enhance its solubility and dissolution. The Biopharmaceutical System of Classification (BCS) II drugs are poorly soluble and have high permeability. Though their good ability to permeate through the membrane make them clinically useful but the problem associated with the solubility restrict their clinical use. Therefore, there is need to improve the solubility of such drug molecules to get effective pharmacological action. Itraconazole (ITZ) is an antifungal agent used in the treatment of fungal infections having poor aqueous solubility as belonging to BCS class II. The present study was aim to enhance the solubility of ITZ by solid dispersion and co-crystallization techniques. Investigation of simultaneous effect of media composition on drug dissolution was also the objective of this work. The ITZ-SD and ITZ-CCs were prepared from ITZ and other excipients like PEG 4000, oxalic acid, fumaric and malic acid by solvent evaporation, kneading technique, slurry conversion and solvent drop grinding methods. The prepared ITZ-SD, ITZ-OA-CCs, ITZ-FA-CCs and ITZ-MA-CCs were evaluated for FTIR, DSC, PXRD, % yield, micromeritic properties. The optimized ITZ-SD and ITZ-CCs were used to compress a tablet and subject to post-compression parameters. The results of FTIR and DSC showed the absence of interaction between the drug and excipients. The PXRD pattern demonstrated the formation of crystalline structures with 6 folds increased in solubility during saturation solubility analysis. In vitro dissolution was carried out in dissolution media with different pH which shows the maximum release from ITZ-SD and ITZ-CCs in pH 6.8. This also revealed the highly pH dependent solubility and dissolution behavior of the weakly basic BCS class II drug (ITZ) with pKa value of 3.7. The overall results in this study indicated the potential of solid dispersion and co-crystals for enhancement of solubility of the poorly water-soluble drugs.

Comparative study of encapsulated cannabidiol ternary solid dispersions prepared by different techniques: The application of a novel technique jet milling

Jet milling is a common technique in ultrafine powder preparation field. It has never been used to design delivery systems. Cannabidiol (CBD) is an important cannabinoid of hemp but poor aqueous solubility limited its applications. In this study, solid dispersion (SD) technique was combined with cyclodextrin complexation technique, and jet milling was used for the first time to prepare SDs for improving CBD solubility. Different characterizations demonstrated that the dispersion effect and complexation structure of CBD SD3 prepared by jet milling were comparable to that of CBD SD2 prepared by spray drying (a common solution-based method), and were better than that of CBD SD1 prepared by cogrinding. The water solubility of CBD was increased to 20.902 μg/mL (909-fold) in CBD SD3. Besides, the antioxidant activity and cytotoxicity to tumor cells of CBD were enhanced by dispersion. This work indicated that jet milling, as a new technique with low cost and excellent applicability, could be further developed for the delivery of food functional factors or bioactive molecules.

Design of mirtazapine solid dispersion with different carriers’ systems: optimization, in vitro evaluation, and bioavailability assessment

The solid dispersion technique is the most effective and widely used approach for increasing the solubility and release of drugs that have low water solubility. Mirtazapine (MRT) is an atypical antidepressant used to treat severe depression. MRT has a low oral bioavailability (about 50%) due to its low water solubility (BCS class II). The study’s goal was to determine optimum conditions for incorporating MRT into various polymer types utilizing the solid dispersion (SD) technique, with the goal of selecting the most suitable formula with the optimal aqueous solubility, loading efficiency, and dissolution rate. The D-optimal design was used to pick the optimal response. The optimum formula was subjected to physicochemical evaluation by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In vivo bioavailability study was conducted on white rabbits’ plasma samples. MRT-SDs were prepared by the solvent evaporation method using Eudragit (RL-100, RS-100, E-100, L-100–55), PVP K-30, and PEG 4000 with different drug/polymer percentages (33.33%, 49.99%, and 66.66%). Results showed that the optimum formula obtained using PVP K-30 at a drug percentage of 33.33% gave a loading efficiency of 100.93%, an aqueous solubility of 0.145 mg/ml, and a dissolution rate of 98.12% after 30 min. These findings demonstrated promising enhancement of MRT properties and increasing its oral bioavailability by 1.34-fold more than plain drug.Graphical

Enhancing the dissolution rate of poorly soluble drug Febuxostat using spray dried amorphous solid dispersion technique

Introduction: Febuxostat belongs to Biopharmaceutical classification system (BCS) class II drugs, which have low solubility and high permeability. Amorphous solid dispersion is one of the techniques which can be useful to improve solubility and powder characteristics.
 Objective: To optimize the concentration of hydrophilic and hydrophobic polymers to improve the dissolution rate and solubility of febuxostat tablets.
 Methods: The amorphous solid dispersion of febuxostat was prepared by spray drying method using Kolliphor P237 (1:2). This amorphous solid dispersion was further used to compress the tablet. To improve solubility and dissolution rate, a full factorial design was applied to optimize the critical concentration of Kollidon SR and hydroxypropyl methyl cellulose (HPMC K4M). The prepared tablets were characterized by pre-compression and post-compression parameters.
 Result: The rate of drug release was sustained by formulating an amorphous solid dispersion technique. The optimized batch (FSRT-OB) was found to be fit for release average 93.30 % of the drug in sustain release manner up to 12hrs. The release kinetic data suggests that the drug release was controlled by combination of diffusion and chain relaxation mechanism. The optimized concentration for Kollidon SR and HPMC K4Mwas found to be 38.50 % and 7.72 % respectively.
 Conclusion: Amorphous solid dispersion technique is useful to enhance solubility, dissolution rate, and bioavailability of the Febuxostat tablet.

Preparation and characterization of fast-release oral film formulation containing ondansetron hydrochloride solid dispersion

Ondansetron has been widely applied as an antiemetic drug in the treatment or prevention of nausea and vomiting caused by emetic cancer chemotherapy . Fast-release films have the advantages of rapid drug release and improved patients’compliance, especially for the disabled bedridden, the elderly or pediatric patients.The basic film-forming materials were studied through single factor tests and the crystal inhibitors were optimized using solid dispersion technique. The ratio of drug and polymers were optimized by X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) which revealed there was no presence of crystal in the optimized solid dispersion. The final film was white thin films and was smooth in surface without obvious bubbles or cracks. Mean weight of each film was 40~50mg. Mean thichness was 60~70μm. Surface pH was 6.4~6.6. The films could release 85% of drug with 1.5min in 0.1mol/L HCl and within 30min in pH6.8PBS. Pharmacolinetic experiment of Ondansetron Hydrochloric solution, marketed films Zuplenz® and the preparation were carried out in rats. As a result, the films of Ondansetron Hydrochloric containing ondansetron solid dispersion had the advantages of fast drug release, improved patient compliance, higher bioavalibility compared to oral solution and the marketed films.

An investigation into solubility and dissolution improvement of alectinib hydrochloride as a third-generation amorphous solid dispersion

Poorly water-soluble drugs belonging to BCS Class II and IV present a big challenge to formulators owing to their limited solubility and bioavailability. Alectinib hydrochloride (ALB), a BCS IV molecule, shows very low solubility resulting in low bioavailability. The objective of the present study is to improve the solubility and dissolution of ALB using the Amorphous Solid Dispersion (ASD) technique. Different polymers and surfactants were screened for solubility enhancement of ALB. Soluplus, as a polymer showed the highest solubility enhancement. ALB and Soluplus in 1:5 ratio resulted in significant improvement in solubility and dissolution when evaluated as a second-generation solid dispersion. The inclusion of 5% P407, a third-generation ASD (ALB-TgSD-P5%), resulted in a further increase in solubility and dissolution. The optimized formulation showed a 2-fold increase in dissolution in FaSSIF, bio-relevant media, indicating the potential for bioavailability improvement. DSC and p-XRD showed the conversion of crystalline drug to amorphous state. Further, FTIR and molecular docking studies showed intermolecular interaction between ALB and Soluplus, thus, providing physical stability for ASD. Stability studies showed the formulation to be stable until 12 months at room temperature with no impact on amorphicity and dissolution. These studies revealed that the low solubility and dissolution concern of Alectinib hydrochloride can be addressed using ASD technique. Third-generation ASD demonstrates superiority over second-generation ASD to improve solubility and dissolution. Improvement of solubility and dissolution in bio-relevant media opens a promising path for clinical evaluation. The optimized formulation is stable and can be easily scaled up for industrial application.

Improved drug transfer into brain tissue via the “nose-to-brain” approach using suspension or powder formulations based on the amorphous solid dispersion technique

Intranasal administration has attracted increasing attention as a drug delivery approach based on nose-to-brain drug delivery from the nasal cavity to brain tissue directly, bypassing the blood–brain barrier. However, application of the method to poorly water-soluble drugs is potentially limited due to low aqueous solubility and dissolution, which can hinder drug transfer to brain tissue. In the present study, we focused on an amorphous solid dispersion (ASD) technique to improve drug dissolution. A carbamazepine-loaded ASD model drug was prepared using the solvent evaporation method (ASD-1). After screening six water-soluble polymer carriers, polyvinyl alcohol (PVA)-based ASD-1 formulation exhibited the most rapid and highest drug dissolution under experimental conditions in the nasal cavity (pH 6.0). A carbamazepine suspension dispersed with a PVA-ASD-1 formulation exhibited enhanced drug delivery into plasma and brain tissue of rats in vivo. A spray-dried powder formulation of PVA-ASD (PVA-ASD-2) exhibited improved drug dissolution and in vivo drug transfer. Our key finding is that the spray-dried PVA-ASD-2 formulation exhibited higher brain/plasma ratios than the PVA-ASD-1 suspension formulation. Our physical characterization data and demonstration of improved drug transfer suggest that ASD-based intranasal formulations hold promise for drug delivery to the brain.

NbCl5 Functionalized Perlite: A Potent and Recyclable Catalyst for Synthesis of Pyrans

Niobium pentachloride functionalised perlite was prepared via a solid state dispersion technique, which was utilized as an efficient heterogeneous catalyst for the synthesis of pyrans. The immobilisation of NbCl5 over perlite was examined by Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Thermogravimetric analysis (TGA), scanning electron microscope (SEM) with energy dispersive spectra (EDS), and Brunauer, Emmett and Teller (BET) surface area measurements. The wt% of NbCl5-loaded perlite was optimized based on the adequacy with respect to the yield of the pyrans in various solvents. The recyclability of the catalyst was validated in synthesizing pyrans and the results marked its efficiency up to five runs. The efficacy of the NbCl5/perlite catalyst was found to be comparable and better with respect to the other heterogeneous catalysts reported. The structures of pyrans were confirmed by FT-IR, 1H and 13C NMR spectral techniques. The proposed recyclable heterogeneous NbCl5/perlite catalyst simplifies the protocol, and has minimal chemical waste, a lower reaction time and a high-yield.

An Innovative Approach for Formulation of Rutin Tablets Targeted for Colon Cancer Treatment

The aim of this study was the improvement of rutin solubility along with targeting its release to colon for effective treatment of colon cancer. Five formulations of compression-coated tablets were prepared with the same core composition including rutin-polyvinyl pyrrolidone K30 solid dispersion (rutin-PVP K30 SD) but differ in being coated with either frankincense alone or different combinations of frankincense with gelatin. The superior formula was selected based on the in vitro drug release then further evaluated in terms of physical properties and in vivo performance in dogs using X-ray. Moreover, in vitro cytotoxicity of rutin, rutin-PVP K30 SD, frankincense, and a mixture of rutin-PVP K30 SD with frankincense in a ratio representing their concentrations in the selected formula was assessed against human colon cancer (HCT-116) cell lines using sulforhodamine B assay. The formula (F4) with the coat consisted of 65%w/w frankincense and 35%w/w gelatin achieved acceptable in vitro controlled drug release. In vivo X-ray in dogs confirmed that F4 tablet could remain intact in the stomach and small intestine until reaching the colon. In vitro cytotoxicity revealed that mixture of rutin-PVP K30 SD with frankincense was more effective in arresting cancer cell growth than rutin or frankincense alone. Moreover, stability studies revealed that F4 tablets were physically and chemically stable. Thus, improving rutin solubility using solid dispersion technique and formulating it into frankincense-based compression-coated (F4) tablets would be a successful approach for colonic delivery of rutin with potential of improving therapeutic efficacy.Graphical

Solubility Enhancement of Carvedilol by Solid Dispersion Technique Using Sodium Alginate, Guar Gum, Xanthan Gum, and Locust Bean Gum as Polymers

Carvedilol (CVD) is a non-selective β-blocker. CVD is included in BCS class II. It has low water solubility. In this research, solid dispersion was used to increase the solubility and dissolution profile of CVD. In silico study using the ligand-ligand docking method. The preparation of solid dispersion using the kneading method with a weight ratio of 1:1, 1:2, 1:3, and 1:4, evaluation of solid dispersion includes solubility and dissolution. The best solid dispersion was characterized using FTIR, DSC, and PXRD. In silico study showed complexes CVD-SA, CVD-GG, CVD-XG and CVD-LBG have a hydrogen interaction. SA and XG were chosen as carriers in solid dispersion. CVD solid dispersion showed increased solubility in all samples, with the highest increase at 90.63 times at CVD: XG (1:4). The results of the dissolution profile obtained at 60 min are 64.95 ± 0.45% at pure CVD, 83.32 ± 1.19% at CVD:SA (1:4), and 72.56 ± 3.62% at CVD: XG (1:4). The FTIR spectrum indicates an interaction between CVD and SA. The thermogram indicated the amorphous drug, and the diffractogram showed a decrease in crystallinity. Solid dispersion is proven to increase the solubility and dissolution profile of CVD. Solid dispersion CVD: SA (1:4) showed the highest solubility and dissolution profile.

Formulation and evaluation of atorvastatin tablets by solid dispersion technique

Formulation and evaluation of atorvastatin tablets by solid dispersion technique