Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir

Hassan, Haniza; Adam, Siti Khadijah; Alias, Ekram; Affandi, Meor Mohd Redzuan Meor Mohd; Shamsuddin, Ahmad Fuad; Basir, Rusliza

doi:10.3390/molecules26185432

Cited by 37 publications

(22 citation statements)

References 51 publications

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“…The design, however, does not include any of these value groups. CCDs (central composite designs) are fractional factorial or factorial designs with axial (star) points amplified by center points that allow curvature evaluation [ 14 ]. The number of star points in a central composite design is always twice as many as the number of components in the plan.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Plant for Colorectal Cancer Prediction and Prevention Using In Silico Molecular Analysis; HOT-MELT Extrusion

Mohamed¹,

Kavitha

Ahmad

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The impact of a soluble complex (SC) of curcumin (CuR) synthesized using hot melt (HM) and hot-melt extrusion (HE) technologies on adenocarcinoma cells for the treatment of colorectal cancer by enhancing CuR solubility is investigated in this work. In silico molecular modelling, solubility, drug release, and physicochemical analysis were all part of the phase solubility (PS) study, which featured a novel dyeing test and a central composite design to optimize the best complex (CDD). The optimal HE-SC (1 : 5) enhances solubility (0.8521 ± 0.016 mg·mL−1) and dissolution (91.87 ± 0.208% at 30 min), and it has an ideal stability constant (309 and 377 M−1) at 25 and 37°C and an AL type of isotherm, implying 1 : 1 stoichiometry according to the findings. An intermolecular hydrogen bond that has not undergone any chemical change and has resulted in the complete conversion of the amorphous form aids in the creation of SC. In vitro cytotoxicity was measured at IC50 on the SW480 (72 M·mL−1) and Caco-2 (40 M·mL−1) cells. According to apoptotic studies, apoptosis was responsible for the vast majority of cell death, with necrosis accounting for a small proportion of the total. In vivo toxicity was established using a zebrafish model, and a western blot examination revealed apoptosis at the molecular level. It was argued that the novel formulations developed using HE technology are more significant and effective than existing pure CuR formulations.

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Section: Introductionmentioning

confidence: 99%

Curcumin Plant for Colorectal Cancer Prediction and Prevention Using In Silico Molecular Analysis; HOT-MELT Extrusion

Mohamed¹,

Kavitha

Ahmad

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The optimized formulation was prepared using the emulsion-gelation technique, and the actual values of the responses were 98.84% for entrapment efficiency, 11.25 h for in vitro buoyancy, and 67.76% for drug release Q6h. it was found that the actual values were found to be close to the predicted values, which indicated the validity of the central composite design [ 52 ].…”

Section: Resultsmentioning

confidence: 82%

Optimization and In Vitro Characterization of Telmisartan Loaded Sodium Alginate Beads and Its In Vivo Efficacy Investigation in Hypertensive Induced Animal Model

et al. 2023

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Background: Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. Methods: For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. Results: The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. Conclusions: It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation’s extended anti-hypertensive activity in animal models.

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“…The behavior of the response surface was evaluated for the selected response function (dependent variable) using a polynomial equation. The equation below describes the generalized response surface model, wherein y stands for the predicted response; β 0 is constant, and β 1 and β 2 are the linear, quadratic, and interaction coefficients, respectively [ 37 ]. Y i = β 0 + β 1 x 1 + β 2 x 2 + β 11 x 1 2 + β 22 x 2 2 + β 12 x 1 x 2 …”

Section: Methodsmentioning

confidence: 99%

Peptide Engraftment on PEGylated Nanoliposomes for Bone Specific Delivery of PTH (1-34) in Osteoporosis

et al. 2023

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Bone-specific functionalization strategies on liposomes are promising approaches to delivering the drug in osteoporotic conditions. This approach delivers the drug to the bone surface specifically, reduces the dose and off-target effects of the drug, and thereby reduces the toxicity of the drug. The purpose of the current research work was to fabricate the bone-specific peptide conjugated pegylated nanoliposomes to deliver anabolic drug and its physicochemical evaluations. For this, a bone-specific peptide (SDSSD) was synthesized, and the synthesized peptide was conjugated with a linker (DSPE-PEG2000-COOH) to obtain a bone-specific conjugate (SDSSD-DSPE). Purified SDSSD-DSPE was characterized by HPLC, Maldi-TOF, NMR, and Scanning Electron Microscope/Energy Dispersive Spectroscopy (SEM/EDS). Further, peptide-conjugated and anabolic drug-encapsulated liposomes (SDSSD-LPs) were developed using the ethanol injection method and optimized by Central Composite Design (CCD) using a statistical approach. Optimized SDSSD-LPs were evaluated for their physicochemical properties, including surface morphology, particle size, zeta potential, in vitro drug release, and bone mineral binding potential. The obtained results from these studies demonstrated that SDSSD-DSPE conjugate and SDSSD-LPs were optimized successfully. The particle size, % EE, and zeta potential of SDSSD-LPs were observed to be 183.07 ± 0.85 nm, 66.72 ± 4.22%, and −25.03 ± 0.21 mV, respectively. SDSSD-LPs demonstrated a sustained drug release profile. Further, the in vitro bone mineral binding assay demonstrated that SDSSD-LPs deliver the drug to the bone surface specifically. These results suggested that SDSSD-LPs could be a potential targeting approach to deliver the anabolic drug in osteoporotic conditions.

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Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir

Cited by 37 publications

References 51 publications

Curcumin Plant for Colorectal Cancer Prediction and Prevention Using In Silico Molecular Analysis; HOT-MELT Extrusion

Curcumin Plant for Colorectal Cancer Prediction and Prevention Using In Silico Molecular Analysis; HOT-MELT Extrusion

Optimization and In Vitro Characterization of Telmisartan Loaded Sodium Alginate Beads and Its In Vivo Efficacy Investigation in Hypertensive Induced Animal Model

Peptide Engraftment on PEGylated Nanoliposomes for Bone Specific Delivery of PTH (1-34) in Osteoporosis

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