Water-insoluble Drugs Research Articles

Design of Spherical Crystallization for Drugs Based on Thermal-Induced Liquid–Liquid Phase Separation: Case Studies of Water-Insoluble Drugs

Spherical crystallization of water-insoluble drugs was investigated based on thermal-induced liquid–liquid phase separation (TILLPS) without the use of organic solvent. The phase diagram of the dru...

Self-microemulsion Technology for Water-insoluble Drug Delivery

: According to the drug discovery, approximately 40% of the new chemical entities show poor bioavailability due to their low aqueous solubility. In order to increase the solubility of the drugs, self-micro emulsifying drug delivery systems (SMEDDS) are considered as an ideal technology for enhancing the permeability of poorly soluble drugs in GI membranes. The SMEDDS are also generally used to enhance the oral bioavailability of the hydrophobic drugs. At present, most of the self-microemulsion drugs are liquid dosage forms, which could cause some disadvantages, such as the low bioavailability of the traditional liquid SMEDDS. Therefore, solid self-micro emulsifying drug delivery systems (S-SMEDDS) have emerged widely in recent years, which were prepared by solidifying a semi-solid or liquid self-emulsifying (SE) ingredient into a powder in order to improve stability, treatment and patient compliance. The article gives a comprehensive introduction of the study of SMEDDS which could effectively tackle the problem of the water-insoluble drug, especially the development of solidification technology of SMEDDS. Finally, the present challenges and the prospects in this field were also discussed.

Role of Structure, Microenvironmental pH, and Speciation To Understand the Formation and Properties of Febuxostat Eutectics.

Cocrystallization studies were undertaken to improve the solubility of a highly water-insoluble drug, febuxostat (FXT), used in the treatment of gout and hyperuricemia. A liquid-assisted grinding (LAG) method was successfully employed, starting with the screening of various coformers for obtaining cocrystals. However, in this process, three eutectic systems with coformers (probenecid, adipic acid, and α-ketoglutaric acid) were formed. Affinities of the different functional groups to form a hydrogen bond and ΔpKa differences, leading to the eutectic formation, were discussed. The eutectic systems thus formed were further characterized and analyzed using a differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD). Binary thermal phase diagrams were plotted using different ratios of the systems to confirm the formation of eutectics, and pH-dependent solubility studies exhibited a significant decrease in the solubility in comparison to that of the drug for all three eutectic systems. The solubility of FXT reduced from 46.53 μg/mL (pH 5.63) to 46.03 μg/mL, 28.53 μg/mL, and 18.88 μg/mL; 770.58 μg/mL (pH 8.21) to 307.574 μg/mL, 116.63 μg/mL, 113.40 μg/mL; and from 13165.97 μg/mL (pH 10.13) to 1409.737 μg/mL, 854.51 μg/mL, and 1218.99 μg/mL for FXT-probenecid, FXT-adipic acid, and FXT-α-ketoglutaric acid eutectic systems, respectively. Furthermore, the microenvironmental pH studies were carried out to understand the effect of the microenvironment on the solubility of these eutectic systems. The contribution to solubility from lattice and nonlattice forces considering the microenvironment was also discussed.

Fluorescent Supramolecular Polymersomes Based on Pillararene/Paraquat Molecular Recognition for pH-controlled Drug Release

Researchers have put significant efforts on developing versatile fluorescent polymeric systems due to their promising biological/biomedical labelling, tracking, monitoring, imaging, and diagnostic applications. However, complicated organic/polymeric synthesis or post-modification of these functionalized platforms is still a big obstacle for their further application and thereby provides clear motivation for exploring alternative strategies for the design and fabrication of easily available fluorescent systems. The marriage of supramolecular polymers and fluorescent imaging can provide a facile and dynamic manner instead of tedious and time-consuming synthesis due to the dynamic and reversible nature of noncovalent interactions. Herein, based on water-soluble pillararene/paraquat molecular recognition, we successfully prepare two amphiphilic polypseudorotaxanes which can self-assemble into supramolecular polymersomes in water. These polymersomes can be reversibly destroyed and reformed by tuning the solution pH. Attributed to the aggregation-induced emission of tetraphenylethylene groups, intense fluorescence can be introduced into the obtained supramolecular polymersomes. Furthermore, pH-triggered release of an encapsulated water-insoluble drug (doxorubicin) from the self-assembled fluorescent supramolecular polymersomes is also investigated.

Formulation and Pharmacokinetic Evaluation of Phosal Based Zaltoprofen Solid Self-Nanoemulsifying Drug Delivery System.

:Background: Phosal based excipients are liquid concentrates containing phospholipids. They are used to solubilize water-insoluble drug and also act as an emulsifier to get the smallest droplet size of the formed emulsion after administration.Objective:The aim is to prepare phosal based self nanoemulsifying drug delivery system (SNEDDS) for water insoluble drug zaltoprofen.Methods: The various parameters like solubility of drug in different vehicles, ternary phase diagram are considered to formulate the stable emulsion which is further characterized by Self emulsification time and globule size analysis to optimize liquid SNEDDS of Zaltoprofen. Optimized L-SNEDDS was converted into free-flowing powder Solid-SNEDDS (S-SNEDDS). S-SNEDDS was evaluated for Globule size analysis after reconstitution, in vitro dissolution study and in vivo pharmacokinetic study in rats.Results: Phosal 53 MCT with highest drug solubility was used as oil along with Tween 80 and PEG 400 as surfactant and cosurfactant respectively to prepare liquid SNEDDS. Neusilin us2 was used as an adsorbent to get free-flowing S-SNEDDS. S-SNEDDS showed improved dissolution profile of the drug as compared to pure drug. In vivo study demonstrated that there is a significant increase in Cmax and AUC of S-SNEDDS compared to zaltoprofen powder.Conclusion:Phosal based SNEDDS formation can be successfully used to improve the dissolution and oral bioavailability of poorly soluble drug zaltoprofen.

FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF LORATADINE SOLID DISPERSION USING SUPER DISINTEGRANTS

The aim of the present investigation was to prepare solid dispersion (SD) of the water insoluble drug. Loratadine using super disintegrants as carrier and formulate it as fast dissolving tablets (FDTs) with an objective to improve solubility and enhance dissolution of drug. The SD’s of the drug were prepared by melt dispersion technique using polyethylene glycol (PEG) 6000 in diferent ratios 1 : 2.5, 1 : 5 and 1 : 7.5. The prepared SD formulations were characterized for equilibrium solubility, Fourier Transform Infrared spectroscopy (FTIR) and in vitro dissolution study. The batch containing SD formulation of loratadine showed fastest dissolution (99.87% drug release in 60 min). In this study, fast dissolving tablets were prepared by direct compression method using Croscarmellose sodium, sodium starch glycolate and polyplasdone XL as the super disintegrants. Effect of various super disintegrants on dissolution behavior of tablets was evaluated in phosphate buffer pH 6.8.

Predicting physical stability of solid dispersions by machine learning techniques

Amorphous solid dispersion (SD) is an effective solubilization technique for water-insoluble drugs. However, physical stability issue of solid dispersions still heavily hindered the development of this technique. Traditional stability experiments need to be tested at least three to six months, which is time-consuming and unpredictable. In this research, a novel prediction model for physical stability of solid dispersion formulations was developed by machine learning techniques. 646 stability data points were collected and described by over 20 molecular descriptors. All data was classified into the training set (60%), validation set (20%), and testing set (20%) by the improved maximum dissimilarity algorithm (MD-FIS). Eight machine learning approaches were compared and random forest (RF) model achieved the best prediction accuracy (82.5%). Moreover, the RF models revealed the contribution of each input parameter, which provided us the theoretical guidance for solid dispersion formulations. Furthermore, the prediction model was confirmed by physical stability experiments of 17β-estradiol (ED)-PVP solid dispersions and the molecular mechanism was investigated by molecular modeling technique. In conclusion, an intelligent model was developed for the prediction of physical stability of solid dispersions, which benefit the rational formulation design of this technique. The integrated experimental, theoretical, modeling and data-driven AI methodology is also able to be used for future formulation development of other dosage forms.

Alginate membrane dressing toughened by chitosan floccule to load antibacterial drugs for wound healing

Transparent and flexible alginate-based membranes containing antibacterial drugs were prepared by a casting/solvent evaporation method from alginate solution mixed with chitosan floccule (CSF) and oxidized sodium alginate (OAlg). To improve the properties of the membranes, CSF and OAlg were added to the alginate solution in different ratios. The mechanism of membrane formation is attributed to two aspects: Schiff-base cross-linking between CSF and OAlg; ion cross-linking between sodium alginate and CaCl2. The results showed that the incorporation of CSF and OAlg had a significant effect on the properties of the alginate membrane. With the change in the ratio between CSF and OAlg, the tensile strength, swelling rate, water vapor permeability, wettability and degradation stability of the membranes were significantly changed. In order to enhance the anti-bacterial properties, clindamycin (DA) and silver sulfadiazine (AgSD), which represent water-soluble and water-insoluble drug models, were integrated into the membrane, respectively. The results of controlled release effects and inhibition zones indicate that the alginate membranes containing drugs have a promising future in treatment of bacterial infection as wound dressing.

Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Emerging Lipid Based Drug Delivery Systems

In the past decade, research in the area of nanodrug delivery has reached a new height with the advent of lipid based nanodrug delivery systems. Lipids being biocompatible and possessing diverse physicochemical properties have tremendous potential to enhance oral bioavailability of water insoluble drugs. Incorporation of a drug in lipid carriers is a smart approach to overcome problems related with conventional oral therapy. In recent years, two lipid based nanoparticles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are widely explored. SLN are spherical nanoparticles with a drug-containing solid lipid core stabilized with surfactants and formulated mainly to improve bioavailability of the drug molecules. Despite several advantages of SLNs, their major drawbacks include limited drug loading, drug leakage, and crystallization during storage. These drawbacks were avoided or reduced by the development of a new generation of lipid nanoparticles, the NLC, wherein a solid lipid is blended with liquid lipid. Modulation of drug release was added advantage with NLC formulations. The present review focuses on production techniques, characterization, release characteristics, stability, toxicity and potential applications of SLNs and NLCs.

Preparation and evaluation of phosphate binding capacity of micronized lanthanum carbonate formulation

The aim of this study was to prepare lanthanum carbonate formulations and to investigate the effects of particle size reduction of lanthanum carbonate to the submicron/micron (SM/M) range by ball milling process. It is a common way to enhance the dissolution rate and therefore the bioactivity of poorly water soluble or insoluble active drug substances by using nanotechnological methods. For this purpose, one of the methods is to prepare drug microcrystals/nanocrystals by decreasing the particle size and thus, increasing the surface area for enhancement of dissolution rate and bioactivity. For this purpose, assay analysis, in-vitro dissolution rates and bioactivity of the formulations were investigated. Assay and in-vitro dissolution rate were analysed by a validated complexometric titration method. Phosphate binding and equilibrium binding studies within the scope of bioactivity studies were carried out by a validated ion chromatography. As a result of these experiments, the phosphate binding capacity and dissolution rate of SM/M lanthanum formulation were found to be higher than both lanthanum formulation (prepared by untreated lanthanum carbonate) and the reference product-Fosrenol® 1000 mg Sachet.

Development and evaluation of PLA-coated co-micellar nanosystem of Resveratrol for the intra-articular treatment of arthritis.

Arthritis is a chronic degenerative joint disease decreasing the patient's quality of life. Mixed micellar system (MM) was exploited as a nanotechnology platform suitable for the encapsulation of the water-insoluble drug, Resveratrol (RES). MM were prepared using different ratios of poloxamer 188 (P188) and poloxamer 407 (P407), and then subjected to in-vitro evaluation. The selected MM (MM3) composed of P188: P407 in a ratio of 2:1 attained the most compromised properties (Particle size = 52.97 ± 4.52 nm, Encapsulation Efficiency = 76.20 ± 4.51 and Release efficiency = 76.26 ± 6.25), and was coated with poly-lactic acid (PLA). TEM photographs of PLA-coated MM3 showed a polymeric layer surrounding the nanoparticles. Rats with induced arthritis were used to study the curative effect of intra-articularly (IA)-injected MM3, PLA-coated MM3 as well as the drug suspension. All the treated groups showed a significant therapeutic improvement in arthritis proved by measuring rats knee diameter as well as the tumor necrosis factor-alpha (TNF-α). The treatment effectiveness was in the following order: PLA-coated MM3 ˃ MM3 ˃ drug suspension, (p < 0.05). Histological study showed the recovery of the joints and synovial structure by IA administration of the drug-loaded micellar nanosystems, and the PLA-coated MM attained the best effect. This study proves the promising curative effect of the designed nanotechnology-based drug carrier.

Investigation of Nanodrug Phospholipovit by Small-Angle Neutron Scattering

The structure of aqueous solutions of the Phospholipovit medicine, intended for transport of water-insoluble molecular drugs, has been investigated by small-angle neutron scattering. Phospholipovit can also be used alone, for example, in case of acute poisoning. When processing experimental data, neutron reflectometry was additionally applied to determine the scattering characteristics of maltose buffer solutions in which the medicine is stored. It is shown that Phospholipovit forms temperature-resistant (in the range of 20–37°C) vesicles of critically small size, with inner radius (~40 A) comparable with lipid bilayer thickness (~31 A), in these solutions. The sensitivity of vesicle parameters to an increase in the medicine concentration in solution (up to 25 wt %) and the character of vesicle interaction (indicating the presence of a significant charge on their outer surface) are determined.

Pyrrolidone-modified PAMAM dendrimers enhance anti-inflammatory potential of indomethacin in vitro

The therapeutic effect of indomethacin, a water-insoluble non-steroidal anti-inflammatory drug, requires its efficient transport through cellular membranes and accumulation inside the target cells. The application of dendritic polymers has been proposed for the improvement of the drug’s solubility and intracellular delivery. In this study we evaluated the anti-inflammatory potential of novel, highly-biocompatible 4-carbomethoxypyrrolidone-coated PAMAM dendrimers loaded with indomethacin. Our results indicate that complexation with dendrimers do not hamper the inhibitory action of indomethacin towards cyclooxygenases. Drug-dendrimer formulations exhibited improved anti-inflammatory activity in in vitro-cultured cellular models, showing enhanced inhibition of prostaglandin secretion and significantly decreased expression of NF-κB marker genes compared to free drug.

In Vitro and In Vivo Evaluation of Core–Shell Mesoporous Silica as a Promising Water-Insoluble Drug Delivery System: Improving the Dissolution Rate and Bioavailability of Celecoxib With Needle-Like Crystallinity

The objective of our study was to prepare mesoporous silica nanoparticles with a core–shell structure (CSMSNs) and improve the dissolution and bioavailability of celecoxib (Cxb), a water-insoluble drug, by changing its needle-like crystal form. CSMSNs are prepared by a core-shell segmentation self-assembly method. The SBET and Vt of CSMSNs were 890.65 m2/g and 1.23 cm3/g, respectively. Cxb was incorporated into CSMSNs by the solvent evaporation method. The gastrointestinal irritancy of the CSMSNs was evaluated by a gastric mucosa irritation test. In vitro dissolution and in vivo pharmacokinetic tests were carried out to study the improvement in the dissolution behavior and oral bioavailability of Cxb. In conclusion, gastric mucosa irritation study indicated the good biocompatibility of CSMSNs. The cumulative dissolution of CSMSNs-Cxb is 86.2% within 60 min in SIF solution, which may be ascribed to the crystal form change caused by control of the nanochannel for CSMSNs. Moreover, CSMSNs could enhance the 9.9-fold AUC of Cxb. The cumulative dissolution and bioavailability of Cxb were both significantly enhanced by CSMSNs. CSMSNs with a core–shell structure are suitable as a carrier for a poorly water-soluble drug (Cxb).

Activity and Cell-Death Pathway in Leishmania infantum Induced by Sugiol: Vectorization Using Yeast Cell Wall Particles Obtained From Saccharomyces cerevisiae.

Visceral leishmaniasis, caused by Leishmania infantum, is a neglected tropical disease, to which efforts in the innovation of effective and affordable treatments remain limited, despite the rising incidence in several regions of the world. In this work, the antileishmanial effects of sugiol were investigated in vitro. This compound was isolated from the bark of Cupressus lusitanica and showed promising activity against L. infantum. In spite of the positive results, it is known that the compound is a poorly water-soluble diterpene molecule, which hinders further investigation, especially in preclinical animal studies. Thus, in an alternative delivery method, sugiol was entrapped in glucan-rich particles obtained from Saccharomyces cerevisiae yeast cell walls (YCWPs). To evaluate the activity of sugiol, the experiments were divided into two parts: (i) the in vitro investigation of antileishmanial activity of free sugiol against L. infantum promastigotes after 24, 48, and 72 h of treatment and (ii) the evaluation of antileishmanial activity of sugiol entrapped in glucan-rich particles against intracellular L. infantum amastigotes. Free sugiol induced the cell-death process in promastigotes, which was triggered by enhancing cytosolic calcium level and promoting the autophagy up to the first 24 h. Over time, the presence of autophagic vacuoles became rarer, especially after treatment with lower concentrations of sugiol, but other cellular events intensified, like ROS production, cell shrinkage, and phosphatidylserine exposure. Hyperpolarization of mitochondrial membrane potential was found at 72 h, induced by the mitochondria calcium uptake, causing an increase in ROS production and lipid peroxidation as a consequence. These events resulted in the cell death of promastigotes by secondary necrosis. Sugiol entrapped in glucan-rich particles was specifically recognized by dectin-1 receptor on the plasma membrane of macrophages, the main host cell of Leishmania spp. Electron micrographs revealed particles containing sugiol within the infected macrophages and these particles were active against the intracellular L. infantum amastigotes without affecting the host cell. Therefore, the YCWPs act like a Trojan horse to successfully deliver sugiol into the macrophage, presenting an interesting strategy to deliver water-insoluble drugs to parasitized cells.

MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan.

To investigate the mechanism of enhancing solubility and bioavailability of water-insoluble drug, valsartan(VAL), with beingmega-loaded by cyclodextrin metal organic framework (CD-MOF). VAL was successfully mega-loaded into CD-MOF by magnetic agitation of VAL in ethanolic solution. Characterizations including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), synchrotron radiation-based Fourier transform-infrared spectroscopy (SR-FTIR) 13C solid-state nuclear magnetic resonance spectroscopy ( 13C SS-NMR), nitrogen gas adsorption, and small-angle X-ray scattering (SAXS) were carried out to confirm the mechanism and incorporation behavior of VAL in CD-MOF. Ball milling process combined with molecular modeling was also used to confirm the mechanism. Improvement of bioavailability in vivo was confirmed by pharmacokinetic experiment in beagles. As a carrier with payload 150% higher than conventional CD complexation, CD-MOF included molecules of VAL as complexations in the chambers of (γ-CD)2, and nanoclusters in the confined spherical cages of (γ-CD)6 confirmed by SAXS and 13C SS-NMR. Ball milling combined with molecular modeling inferred that the reduced release rate of the milled CD-MOF with ultrahigh drug payload was mainly due to the partial aggregation of the VAL nanoclusters. The molecules of VAL as nanoclusters in the cages of (γ-CD)6 are critical in dramatically improving theapparent solubility (39.5-fold) and oral bioavailability (1.9-fold) of VAL in contrast to γ-CD inclusion. The new understanding of drug nanoclusters in CD-MOF will help to design more efficient drug delivery systems using CD-MOF carrier with nanocavities.

A Comparative Study of the Use of Mesoporous Carbon and Mesoporous Silica as Drug Carriers for Oral Delivery of the Water-Insoluble Drug Carvedilol.

Mesoporous carriers have been extensively applied to improve the dissolution velocity and bioavailability of insoluble drugs. The goal of this work was to compare the drug-loading efficiency (LE) and drug-dissolution properties of mesoporous silica nanoparticles (MSN) and mesoporous carbon nanoparticles (MCN) as drug vectors oral delivery of water-insoluble drugs. For this purpose, MSN and MCN with similar particle size, surface area, and mesoporous diameter were prepared to precisely evaluate the effects of different textures on the drug-loading and dissolution behavior of insoluble drugs. Carvedilol (CAR), a Bio-pharmaceutic Classification System (BCS) class II drug, was loaded in the MSN and MCN by the solvent adsorption method and solvent evaporation method with different carrier–drug ratios. The carboxylated MCN (MCN–COOH) had a higher LE for CAR than MSN for both the two loading methods due to the strong adsorption effect and π–π stacking force with CAR. In vitro drug dissolution study showed that both MSN and MCN-COOH could improve the dissolution rate of CAR compared with the micronized CAR. In comparison to MSN, MCN-COOH displayed a slightly slower dissolution profile, which may be ascribed to the strong interaction between MCN-COOH and CAR. Observation of cell cytotoxicity and gastrointestinal mucosa irritation demonstrated the good biocompatibility of both MSN and MCN–COOH. The present study encourages further research of different carriers to determine their potential application in oral administration.

Synthesis of luteolin loaded zein nanoparticles for targeted cancer therapy improving bioavailability and efficacy

A naturally occurring flavonoid, Luteolin possess wide range of pharmaceutical activities from anti-inflammatory to anticancer effect. Luteolin inhibits cell proliferation by arresting cell cycle pathways and triggers apoptotic cell death. Poor aqueous solubility of luteolin limits its oral bioavailability. Therefore, to improve the oral bioavailability of luteolin by use of biodegradable protein zein and sodium caseinate as nanocarrier. The nanoparticles were prepared by simple precipitation process. The resulting nanoparticles had mean size of 200–300 nm with negative zeta potential with 92% encapsulation efficiency and luteolin release at intestinal pH. Anti-oxidant activity of loaded molecule with respect to parent molecule significantly indicate the free radical scavenging potential of luteolin increases after encapsulation in zein nanoparticles. Luteolin loaded zein nanoparticles showed enhanced cytotoxicity against SW480 colon cancer cells and induces apoptosis. In this paper, we have shown the potential of luteolin loaded zein nanoparticles for treating colon cancer which could serve as promising strategy to develop oral formulation of this water insoluble drug enhancing its bioavailability.

Ureasil Organic-Inorganic Hybrid as a Potential Carrier for Combined Delivery of Anti-Inflammatory and Anticancer Drugs.

There continues to be a need to develop controlled-release systems loaded with multiple drugs with distinct pharmacological activities, such as anti-inflammatory and anticancer effects, which are able to provide the desired release of each drug, as a function of time. To this end, an elegant strategy was developed for the incorporation, in a one-step process, of the anti-inflammatory drug naproxen (NAP) and the anticancer drug 5-fluorouracil (5FU) into a ureasil organic-inorganic hybrid matrix. A ureasil-poly(oxyalkylene) (UPEO) matrix was prepared using a sol-gel route to obtain a versatile dual-drug delivery system. Small-angle X-ray scattering (SAXS) measurements and Fourier transform infrared spectroscopy (FTIR) demonstrated that the UPEO network is preserved upon loading with the two drugs NAP and 5FU. There was excellent agreement between the macroscopic swelling behavior (water uptake) and surface wettability (determined using contact angle measurements), with this behavior being closely correlated with the release profiles and playing an important role in the sustained delivery of both drugs from the hybrid matrix. The amounts of both drugs released simultaneously could be finely controlled by adjusting the pH of the aqueous medium, with the release presenting stimulus-responsive behavior. In an aqueous PBS medium, the dual-UPEO-release system presented excellent potential as a vehicle for the release of the water-soluble 5FU and water-insoluble NAP drugs, at identical rates, using a single carrier. This novel and adjustable dual-drug delivery UPEO system is a promising hybrid material carrier with the ability to simultaneously incorporate a wide range of therapeutic agents for the treatment of various diseases, including cancers.

Synthesis of Silica-Coated Magnetic Hydroxyapatite Composites for Drug Delivery Applications.

We have prepared a core-shell magnetic silica-coated hydroxyapatite, Fe₃O₄@SiO₂@HAp composite materials for pH-responsive drug delivery applications. Captopril (Cap) and ibuprofen (Ibu) were chosen as model hydrophilic and hydrophobic drugs, respectively. The drugs were encapsulated into the Fe₃O₄@SiO₂@HAp composite via electrostatic interactions with existing amine and carboxylic acid groups during calcium phosphate shell formation. The formation of calcium phosphate shell not only protects the encapsulated drugs from leaching but also controls the release rate of drugs from the composite system depending on various pH conditions. We have tested the release behavior of Cap and Ibu drugs under different pH conditions such as neutral pH (pH 7.4) and acidic pH (pH 5.0), respectively. The study result reveals that the synthesized Fe₃O₄@SiO₂@HAp composite is suitable for release of both water soluble and water insoluble drugs based on a pH-responsive controlled manner.