Glyceryl Behenate Research Articles

Tailoring Fumaric Acid Delivery: The Role of Surfactant-Enhanced Solid Lipid Microparticles via Spray-Congealing.

Fumaric acid, a naturally occurring preservative with antimicrobial properties, has been widely used in the baking industry. However, its direct addition interferes with yeast activity and negatively impacts the gluten structure. This study investigates the potential of spray-congealing as a method for encapsulating fumaric acid within solid lipid microparticles. The selection of lipid carriers and surfactants is critical, so hydrogenated palm stearin, hydrogenated rapeseed oil, and Compritol ATO 888 (glyceryl behenate) were chosen as lipid carriers, and propylene glycol monostearate and glyceryl monolaurate were utilised as surfactants with varying concentrations. Rheological properties, encapsulation efficiency, particle size, moisture content, and thermal behaviour were assessed, along with the release profiles under different temperature conditions simulating the baking process. The findings indicate that the addition of surfactants significantly impacts the viscosity and stability of the molten mixtures, which in turn affects the spray-congealing process and the release of fumaric acid. The temperature-dependent and time-dependent release profiles demonstrate the potential for customising release kinetics to suit specific applications, such as the baking industry. This study may contribute to the development of a controlled-release system that synchronises with the baking process, thereby optimising fumaric acid's functionality while preserving the quality of baked goods.

Design and optimization of chitosan-coated solid lipid nanoparticles containing insulin for improved intestinal permeability using piperine

The objective of this research was to optimize the composition and performance of chitosan-coated solid lipid nanoparticles carrying insulin (Ch-In-SLNs) and to assess the potential of piperine in enhancing the intestinal permeability of insulin from these SLNs in vitro. The SLNs were formulated from glyceryl behenate (GB), soya lecithin, and poloxamer® 407, and then coated with a combination of chitosan and piperine to facilitate insulin penetration across the gastrointestinal (GI) mucosa. A Box-Behnken Design (BBD) was utilized to optimize the Ch-In-SLNs formulations, with PDI, particle size, zeta potential, and association efficiency (AE) serving as the response variables. The resulting Ch-In-SLNs exhibited excellent monodispersity (PDI = 0.4), optimal particle size (654.43 nm), positive zeta potential (+36.87 mV), and low AE values. The Ch-In-SLNs demonstrated sustained release of insulin for 12 h in simulated gastric fluid (SGF) and intestinal fluid (SIF), with increased release in the latter. After incubation in SGF and SIF for 12 h, the insulin SLNs retained 54 and 41 % of their initial insulin load, respectively, indicating effective protection from gastric enzymes. Permeation studies using goat intestine and Caco-2 cell lines indicated improved insulin permeation in the presence of piperine. Additionally, cell uptake studies confirmed the role of piperine in enhancing insulin permeation.

Formulation, Optimization, and Evaluation of Ezetimibe for Chronotherapeutic Drug Delivery using Compression-Coating Technology

Objectives: The purpose of the present study was to Formulation, optimization and evaluation of drug for chronotherapeutic drug delivery using compression coating technology for hypercholesterolemia. Material and Methods: The drug delivery system was designed to deliver the drug at a time when it could be needed for the most in the early morning (4 to 6 a.m.) for patients in case of hypercholesterolemia. The pulsatile concept was applied to the dosage form by having a lag phase followed by an immediate release. The prepared system consisted of two parts: a core tablet containing the active ingredient and fracture outer shell with delay-release polymer having diffusion characteristics. Solid dispersion was carried out by screening of betacyclodextrin, Polyvinyl pyrrolidone (PVP K30), and HPMC using three different drug complex ratios 1:1, 1:2, and 1:3 by a solvent evaporation method through spray dryer. The immediate-release core tablet (IRCT) was prepared by using a superdisintegrant with active ingredients. Screening of IRCT was carried out by pre and post compression parameters, disintegration time and an in-vitro dissolution study. The pulsatile release tablet (PRT) of optimized IRCT was made by Glyceryl Behenate and Dibasic Calcium Phosphate. Optimization of polymer concentration of PRT was carried out by pre and post-compression parameters, pulsatile lag time, and an in-vitro dissolution study. A 32 factorial design was employed to optimize the PRT. The design consisted of two dependent variables R1, and R2 independent variables X1 and X2. The two independent formulation variables selected for the study including Concentration of coating polymer and Concentration of lubricant. The dependent variables are Lag Time and Thickness. Results: XRD, DSC and FTIR spectra showed that solid dispersion was formed by the drug and PVP K30 complex. IRCT batch RR1 containing 22mg croscarmellose sodium to achieve good 30sec disintegration time and 98.34% drug release at the end of 20 minutes of Ezetimibe respectively. PRT formulation DR6 showed good pre and post-compression parameters with a satisfactory drug release of 98.34% for Ezetimibe respectively with a lag time of 6 hours. The 32 factorial design was used for the optimization of PRT parameters. A total of 9 experiments were performed for two factors at three levels each. The optimized batch showed 98.27% DR for Ezetimibe in 6.2 hrs (within 20 min after lag time) with pulsatile lag time up to 6.0 hrs and thickness of 5.10 kp. Conclusion: It was concluded that tablet within the tablet, pulsatile drug delivery of Ezetimibe (BCS class-II drugs) was successfully formulated with the advantage of enhanced solubility, and pulsatile release behavior and had an added benefit of suitable for chronopharmacotherapy of diseases that show circadian rhythms in their pathophysiology.

Optimization and evaluation of modified release solid dosage forms using artificial neural network

This study aims to optimize and evaluate drug release kinetics of Modified-Release (MR) solid dosage form of Quetiapine Fumarate MR tablets by using the Artificial Neural Networks (ANNs). In training the neural network, the drug contents of Quetiapine Fumarate MR tablet such as Sodium Citrate, Eudragit® L100 55, Eudragit® L30 D55, Lactose Monohydrate, Dicalcium Phosphate (DCP), and Glyceryl Behenate were used as variable input data and Drug Substance Quetiapine Fumarate, Triethyl Citrate, and Magnesium Stearate were used as constant input data for the formulation of the tablet. The in-vitro dissolution profiles of Quetiapine Fumarate MR tablets at ten different time points were used as a target data. Several layers together build the neural network by connecting the input data with the output data via weights, these weights show importance of input nodes. The training process optimises the weights of the drug product excipients to achieve the desired drug release through the simulation process in MATLAB software. The percentage drug release of predicted formulation matched with the manufactured formulation using the similarity factor (f2), which evaluates network efficiency. The ANNs have enormous potential for rapidly optimizing pharmaceutical formulations with desirable performance characteristics.

Solubility Enhancement of Poorly Water-Soluble Aceclofenac by Amalgamation Micronization and Solid Dispersion Techniques

Aceclofenac is a poorly aqueous soluble Biopharmaceutical Classification System (BCS) class II drug that has bioavailability problems after oral administration due to low aqueous solubility. There are numerous solubility modification approaches and they also have process limitations. Hence, the present research work aims to use two different solubility enhancement techniques (Micronization with Solid dispersion) simultaneously to counter individual limitations of techniques. The micronization technique increases the solubility of pure aceclofenac through increasing particle surface area, but it produces charged micronized material, leading to segregation and clumping of micronized material. Hence, micronized material handling during dosage form manufacturing is quite difficult. In the present research work, aceclofenac material is micronized by air jet mill to produce materials of below 25 μm size ranges. This micronized aceclofenac material is further encapsulated in a solid dispersion technique to produce amorphous aceclofenac materials. Solid dispersion of micronized aceclofenac was prepared by various techniques like physical kneading, solvent evaporation, melting and a combination thereof using different polymers (Polyox 301, HPMC, cetostearyl alcohol and glyceryl behenate). The prepared solid dispersion formulation (SD-31, SD-22, SD-23 and SD-30) exhibited an increase in the dissolution of aceclofenac as compared to pure aceclofenac. Various characterization techniques (Differential scanning calorimetry (DSC), X-ray Diffraction (XRD) and scanning electron microscope (SEM)) also reveal that aceclofenac crystallinity is significantly minimized in Solid dispersion formulation of SD-31, SD-22, SD-23 and SD-30. This selected solid dispersion (SD-31 and SD-22) also exhibited good stability (Photostability and stability at 40°C/75% RH after 3 months).

Thermal Analysis in the Evaluation of Solid Lipid Microparticles in the Form of Aqueous Dispersion and Fine Powder

In the presented study, an attempt was made to investigate the most important attributes of solid lipid microparticles (SLM) using thermal analysis (DSC/TG) in order to determine the importance of this technique in the research and development of lipid microparticles. Particularly interesting in our studies were drug–lipid interactions and modifications of the SLM matrix structure induced by the production method (the hot emulsification method) and further processing (e.g., spray drying), as well as changes occurring during the stability studies. Cyclosporine A, indomethacin and spironolactone were used as model active substances incorporated into SLM. The conducted research demonstrated the significant potential of DSC/TG, especially for the analysis of SLM in the form of fine powder. The method of sample preparation, consisting of evaporation of water at room temperature, turned out to be crucial for the DSC/TG analysis of SLM dispersion. In the case of the tested SLM, the basic and usually the only observed thermal transformation in the DSC spectrum was the endothermic peak associated with the lipid forming a microsphere matrix. This peak is the main source of information about the properties and stability of the tested SLM. The obtained results show that glyceryl behenate (Compritol) is a significantly better lipid for forming lipid microparticles than stearic acid. Although thermal transformations of the incorporated drug substances are not directly visible in the DSC spectra, their impact on the SLM properties can be assessed indirectly, based on changes in the lipid melting point and the shape of the DSC and TG peaks and curves. DSC/TG studies confirmed the lack of an effect of the spray drying process on the properties of drug-loaded SLM with Compritol. Studies have also shown up to a 2-year stability of SLM with CsA.

Bigel Formulations of Nanoencapsulated St. John's Wort Extract-An Approach for Enhanced Wound Healing.

This study aimed to develop a semisolid vehicle for topical delivery of nanoencapsulated St. John's wort (SJW) extract, rich in hyperforin (HP), and explore its wound-healing potential. Four nanostructured lipid carriers (NLCs) were obtained: blank and HP-rich SJW extract-loaded (HP-NLC). They comprised glyceryl behenate (GB) as a solid lipid, almond oil (AO), or borage oil (BO) representing the liquid lipid, along with polyoxyethylene (20) sorbitan monooleate (PSMO) and sorbitan monooleate (SMO) as surfactants. The dispersions demonstrated anisometric nanoscale particles with acceptable size distribution and disrupted crystalline structure, providing entrapment capacity higher than 70%. The carrier exhibiting preferable characteristics (HP-NLC2) was gelled with Poloxamer 407 (PM407) to serve as the hydrophilic phase of a bigel, to which the combination of BO and sorbitan monostearate (SMS) organogel was added. The eight prepared bigels with different proportions (blank and nanodispersion-loaded) were characterized rheologically and texturally to investigate the impact of the hydrogel-to-oleogel ratio. The therapeutic potential of the superior formulation (HP-NLC-BG2) was evaluated in vivo on Wistar male rats through the tensile strength test on a primary-closed incised wound. Compared with a commercial herbal semisolid and a control group, the highest tear resistance (7.764 ± 0.13 N) was achieved by HP-NLC-BG2, proving its outstanding wound-healing effect.

Development And Optimisation Of Magnesium Alumino Metasilicate Loaded Tacrolimus Extended Release Tablets By Qbd Approach For Management Of Oragan Transplantation

The current present study was planned to formulate tacrolimus extended-release tablets to enhance drug activity. Tacrolimus is a calcineurin inhibitor used to treat mild to moderate atopic dermatitis and preclude organ transplant rejection. However, tacrolimus consists of low bioavailability and shorter half-life. Therefore, it was intended to formulate an extended release formulation with suitable polymers to upregulates its therapeutic response.The melt granulation method was used for the preparation of tacrolimus extended release tablets. The central composite design was employed for optimization at two level three factors. Crucial materials properties were the concentration of glyceryl behenate (X1), the concentration of Hypromellose (X2), and the concentration of PEG 6000 (X3).ANOVA has been implemented to interpret the data and design space.The tacrolimus extended release tablet was successfully formulated using melt granulation method and invitro profile of optimized batch compared with marketed formulation. The outcome of the study revealed that optimized formulation of tacrolimus shows 100% release at 12 h. Whereas, marketed formulation (Envarsus XR) also shows 100% release at12 h. Thus, the findings revealed that the optimized formulation was successfully prepared and suitable for extended release nature

Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.

Characterization and in vitro release of inhalation quercetin solid lipid microparticles: Effect of lipid.

This study purposes to develop solid lipid microparticles (SLM) inhalation delivery system for respiratory diseases with Quercetin as the active agent. Quercetin has various functions, such as for antioxidant, anti-inflammatory, immunomodulator, and antivirus. SLM is formed from a mixture of lipids and surfactants, namely, Glyceryl Behenate as solid lipid, Poloxamer 188 as the surfactant, and production of SLM using the melt o/w emulsification technique and was dried using freeze dryer. The effect of lipid concentration was studied in this research. Quercetin SLM was characterized by moisture content, Fourier transform infrared, particle size, yield, drug loading, and encapsulation efficiency. The SLM particles produced were spherical in shape and had a smooth surface with sizes of F1, F2, and F3 were 1.79 μm, 1.88 μm, and 1.91 μm, respectively. According to the target particle size of inhalation, Quercetin SLM had good flowability according to Carr's Index (F1 = 12.73% ± 0.38, F2 = 14.28% ± 0.65, F3 = 14.65% ± 0.62), in which the highest drug loading and EE of F3 were 10.94% and 88.48%, respectively. In vitro release study showed that in 630 min about 31%–33% Quercetin released indicated sustained release following Higuchi kinetics and quercetin release rate was not affected by the amount of lipid. To sum up, quercetin SLM demonstrates its potential as an inhalation delivery system and it is recommended to study its stability.

Development and Evaluation of Extended Release Tacrolimus Tablets by Melt Granulation in Combination with Magnesium Alumino Metasilicate

To increase the effectiveness of tacrolimus, the present study sought to develop extended-release tablets. It is used to treat mild to severe atopic dermatitis as well as to prevent organ rejection after organ transplantation. Tacrolimus, on the other hand, has a poor bioavailability and a short half-life. The current research aims to create extended-release tacrolimus tablets by melting and granulating utilizing lipid and adsorbent materials to ensure excellent flow and a hypromellose matrix system to regulate release for 12 hr. Tacrolimus granules were prepared by melting with glyceryl behenate in rapid mixer granulator in the presence of polyethylene glycol followed by magnesium alumino metasilicate for adsorption purposes. Adsorbed granules were milled, sifted, and mixed with extra granular material such as hypromellose, lactose monohydrate and magnesium stearate. Granules were compressed to tablets using oval-shaped plain tooling. In vitro dissolution profile of solid dispersion and extended release tablets were investigated. Release profile of tablets and solid dispersion were improved by melt granulation due to the polymorphic form conversion of drug substance from crystalline to amorphous.Release kinetics of tacrolimus extended release tablets were fitted with zero order release with R2 value of 0.964, which designate constant release for 12 hr. Therefore, the present findings from the study revealed that the formulation was successfully prepared and showed extended release pattern over 12 hr.

Phase Behavior of Drug-Lipid-Surfactant Ternary Systems toward Understanding the Annealing-Induced Change.

The present study systematically investigates the effect of annealing conditions and the Kolliphor P 407 content on the physicochemical and structural properties of Compritol (glyceryl behenate) and ternary systems prepared via melt cooling (Kolliphor P 407, Compritol, and a hydrophilic API) representing solid-lipid formulations. The physical properties of Compritol and the ternary systems with varying ratios of Compritol and Kolliphor P 407 were characterized using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS) and infrared (IR) spectroscopy, and hot-stage microscopy (HSM), before and after annealing. The change in the chemical profiles of different Compritol components as a function of annealing was evaluated using 1H NMR spectroscopy. While no change in the polymorphic form of API and Kolliphor P 407 occurred during annealing, a systematic conversion of the α- to β-form was observed in the case of Compritol. Furthermore, the polymorphic transformation of Compritol was found to be dependent on the Kolliphor P 407 content. As per the Flory-Huggins mixing theory, higher miscibility was observed in the case of monobehenin-Kolliphor P 407, monobehenin-dibehenin, and dibehenin-tribehenin binary mixtures. The miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin was confirmed by 1H NMR analysis. The observed higher miscibility of Kolliphor P 407 with monobehenin and 1,2-dibehenin is proposed as the trigger for the physical separation from the 1,3-diglyceride and triglycerides during melt solidification of the formulations. The phase separation is postulated as the mechanism underlying the formation of a stable β-polymorphic form (a native form of 1,3-diglyceride) of Compritol upon annealing. This finding is expected to have an important implication for developing stable solid-lipid-surfactant-based drug formulations.

Design, optimization and in-vivo characterization of mupirocin loaded nanostructured lipid carrier based gel for effective treatment of impetigo

Mupirocin is a broad-spectrum antibiotic effective in treatment of skin infection (Impetigo), but the poor bioavailability limits its use as a conventional dosage form such as tablets, ointment and cream. The present investigation was aimed to design, optimize and evaluate Mupirocin (MC) loaded nanostructured lipid carriers (NLCs) based gel for topical application. Excipients identified were screened for apposite material required for the formulation of NLCs using process variables as the determining factors. The preparation of nanostructured lipid carriers (NLCs) was optimized using 32 factorial design with two independent variables (solid: liquid lipid ratio and surfactant (%)) and two responses (particle size (nm), entrapment efficiency (%)) using hot high pressure homogenization method. The formulation was further characterized for zeta potential (mV), polydispersity index and morphology. The optimized NLC dispersion of Mupirocin (MC) was lyophilized and loaded in 0.75% w/v Carbopol 980 gel and was evaluated for pH, viscosity and drug content. Mupirocin (MC) loaded NLC based gel were characterized for ex-vivo drug permeation and compared with marketed (cream) preparation. Further, drug deposition, skin irritation and stability study was carried out as per ICH guidelines. The optimized formulation (F5) containing Glyceryl behenate: Oleic acid (70:30), and Poloxamer 188 (0.5%) demonstrated smaller particle size (150.02 ± 1.52 nm) with higher drug entrapment efficiency (88.02 ± 1.21%). Mupirocin (MC) loaded NLC based gel demonstrated sustained drug profile with significant increase (P < 0.05) in drug deposition in skin (about 26%) with non-irritant properties to the skin. Stability study showed no significant changes of the parameters during and after the study. In conclusion, developed Mupirocin (MC) loaded NLC based gel could serve as a novel approach in treatment of impetigo by deliver the drug topically with sustained effect and improved patient compliance.

Formulation and Evaluation of Solid Lipid Nanoparticles for controlled delivery of Zidovudine

Zidovudine is one of the chief nucleoside analogue and reverse inhibitor licensed for HIV infection which is placed along with a group of retroviruses. The present research study on Zidovudine solid dosage form surveyed the feasibility utilizing solid lipid nanoparticles (SLNs) for controlled drug delivery of zidovudine embracing glyceryl behenate as lipidic material, tween 80 as a stabilizer and blend of sodium chelate with poloxamer as surfactant. The SLNs were prepared utilizing high pressure homogenization followed by ultrasonication method. The prepared SLNs were characterized by particle size analysis, polydispersity index, zeta potential, DSC, TEM, IR spectroscopy, and X-ray diffractometry. Narrow size distribution of the particles was marked having polydispersity index values under 0.8. The high zeta potential of the different SLN formulations additionally showed their physical stability. Differential scanning calorimetry and powder X-ray diffraction showed decline in crystallinity of drug in the nanoparticle formulation. In vitro release study showed sustained release for up to 12 hours in the SLN formulations prepared. The current study results revealed that zidovudine SLN formulation prepared by high pressure homogenization followed by ultrasonication is a suitable method for controlled drug delivery system.

Gamma sterilization and in vivo evaluation of cationic nanostructured lipid carriers as potential ocular delivery systems for antiglaucoma drugs

Solid lipid nanoparticles and nanostructured lipid carriers showed promising results for enhancement of ocular bioavailability of drugs with poor corneal permeability. One of these drugs is methazolamide, which is an orally administered carbonic anhydrase inhibitor for glaucoma treatment. However, sterilization by autoclaving may result in loss of the physical properties of lipid nanoparticles such as particle size and surface charge. Here, we evaluated gamma radiation as an alternative sterilization method. Methazolamide loaded nanostructured lipid carriers were optimized using 23 factorial design. Optimized formulations contained 6% lipid (85% solid lipid (Cetostearyl alcohol and glyceryl behenate) and 15% oil either medium chain triglycerides or isopropyl myristate) stabilized by 2% polysorbate 80 and 0.15% stearylamine. Nanoparticles were cationic, smaller than 500 nm, and had an entrapment efficiency of about 30%. They released methazolamide within 8 hours and showed a 5-fold enhanced reduction in intraocular pressure compared to methazolamide solution. Gamma sterilization was superior to autoclaving in preserving entrapped methazolamide, size, and surface charge of lipid nanoparticles. These findings demonstrate that gamma radiation is a viable alternative to autoclaving for sterilizing lipid nanoparticles. Moreover, this proves that nanostructured lipid carriers enhance pharmacological response of topically administered methazolamide for treating glaucoma.

Design and Investigation of Alginate Coated Solid Lipid Nanoparticles for Oral Insulin Delivery

Abstract: Introduction: The conventional subcutaneous administration of insulin has been associated with several limitations leading to poor patient compliance. The poor oral bioavailability of insulin due to degradation by gastrointestinal enzymes and secretions can be countered by the use of protective carriers such as solid lipid nanoparticles that are capable of being taken up by the Peyer’s patches. The aim of the investigation was to design and investigate alginate coated solid lipid nanoparticles (SLN) of insulin for oral administration. Materials and Methods: The SLN were prepared from glyceryl behenate and glyceryl monostearate and coated with mucoadhesive polymer, sodium alginate. The SLN were evaluated for size, shape, zeta potential, drug content, in vitro release and ex vivo drug permeation through goat intestinal mucosa and Caco-2 cell monolayer model. Results and Discussion: Transmission electron microscopy revealed spherical particles of uniform size distribution. In vitro drug release using the reverse dialysis method revealed that the alginate coating maintained the potency of insulin in simulated GI fluids and also provided sustained release. Absorption enhancement was demonstrated in ex vivo permeation studies in the goat intestinal mucosal model as well as in the Caco-2 cell monolayer model. The oral administration of alginate-coated insulin SLN in streptozotocin induced diabetic rats resulted in a significant hypoglycemic effect as compared to that of uncoated insulin-loaded SLN. The percentage glycemia at the end of 10 h was statistically significant (p<0.05) to oral insulin and the hypoglycemic levels reached were comparable to that of the conventional subcutaneous insulin. Conclusion: Alginate coated SLN has the potential of improving the absorption of insulin through intestinal mucosa and possibly its bioavailability. Key words: Solid lipid nanoparticle, Insulin, Oral delivery, Sodium alginate, Glycerol monostearate, Hypoglycemia.

A New Approach to the Dissolution Tests Management to Obtain Kinetic and Thermodynamic Data: Release of a Model Drug from Glyceryl Behenate Matrix Tablets

AbstractThis study is focused on the use of glyceryl behenate as a lipophilic excipient of matrix tablets providing controlled drug release. The aim of this study is to evaluate activation energy (EA) and changes of the thermodynamic parameters (ΔH, ΔS, ΔG) of a dissolution process. These values, which have not yet been published, can lead to better understanding of a drug release mechanism and can extend the use options of glyceryl behenate in the pharmaceutical industry. Values of ΔH, ΔS, ΔG and EA, providing an overall thermodynamic view on the studied matrix tablets, are evaluated based on the temperature‐dependences of the release rate constant of a model drug (temperature range 25 ‐ 45 °C). The studied lipophilic matrix tablets contain 10% to 50% of glyceryl behenate. Dissolution testing is carried out in an aqueous solution of HCl with addition of NaCl (pH1.2). Positive values of ΔH in the range of 3.83 to 56.13 kJ mol‐1 and positive values of ΔG indicate that the dissolution of the studied glyceryl behenate matrix tablets is an endothermic process which does not proceed spontaneously (in a temperature range of 25 ‐ 45 °C). The negative slope of the linear curves of enthalpy‐entropy compensation confirms the entropy‐driven dissolution.Practical Applications: A better understanding of the dissolution process is an important aspect, e.g., in the field of drug formulation strategy. In this study, it is confirmed that the influence of temperature on the model drug release rate is negligible for tablets containing more than 40% of glyceryl behenate. It is an important result for drug design due to the reduction of risk of a possible dose dumping effect induced by temperature and the prevention of in vivo therapeutic failure.

Optimized semisolid self-nanoemulsifying system based on glyceryl behenate: A potential nanoplatform for enhancing antitumor activity of raloxifene hydrochloride in MCF-7 human breast cancer cells

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator used for treatment and protection against postmenopausal osteoporosis. The drug has been used for protection against breast cancer and more recently, for management of the disease by virtue of its estrogen antagonist action. However, the drug has reduced bioavailability related to low water solubility and first pass metabolism. To surmount these pitfalls, this study aimed at developing and optimizing RLX-loaded semisolid self-nanoemulsifying system (SSNES) with minimized globule size to improve the drug solubility, tumor penetration, and consequently antitumor activity. A simplex lattice mixture design was employed for the formulation and optimization of SSNESs. The mixture components, namely, Compritol® 888 ATO, Tween 20, and polyethylene glycol 200 exhibited significant effect on globule size at P < 0.05. The optimized formulation with globule size of 109.19 ± 2.11 nm showed acceptable thermodynamic stability under stress conditions. Anti-cancer efficacy of the obtained formulation was evaluated in MCF-7 breast cancer cell line. MTT viability assay revealed that RLX-loaded SSNES notably inhibited MCF-7 cell proliferation. Flow cytometry and dual staining with annexin V-FITC/PI were used to assay this anti-proliferative effect and induction of apoptosis, respectively. Cells treated with RLX-loaded SSNES showed significant arrest at G2/M phase associated with significant increase in early/late-stages of apoptotic and necrotic cells. The results exhibited that RLX-loaded SSNES induces apoptosis via the activation of caspase-3 and loss of mitochondrial membrane potential. Accordingly, the proposed SSNES could be regarded as a promising platform for enhancing RLX antitumor activity against breast cancer.

Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ™ 721 (fillers); Plasdone™ S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carr’s index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ™ 721), copovidone (Plasdone™ S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.

Formulation, Characterization and in-vitro Evaluation of Famciclovir Loaded Solid Lipid Nanoparticles for Improved Oral Absorption

Famciclovir loaded Solid Lipid Nanoparticles (SLNs) using triglycerides as solid lipids were successfully prepared using the double emulsion-solvent evaporation technique. Formulation parameters like amount and type of lipid and level of surfactants affected the nanoparticle characters. It was observed that nanoparticle characters like average particle size and distribution, drug content, entrapment efficiency and release pattern were dependent on these formulation variables. The optimized formulations depicted the desired characters of low particle size, in the range of 140-170 nm in case of Glyceryl monostearate (GMS) and glyceryl distearate (GDS) SLNs and 250-340 nm in case of glyceryl behenate (GB) SLNs and entrapment efficiencies in the range of 35-48%. In vitro drug release was extended upto 8 h and the release profile was explained by the Baker-Lonsdale model for spherical particles. Morphological examination by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) displayed homogenous solid, spherical and non- porous particles. The formulations depicted good redispersibility after lyophilization and presence of residual solvents in the formulations within the prescribed limits suggested suitability of the preparation technique. Freeze- dried formulations were found to be stable in terms of particle size and drug loading even after 6 months of storage at refrigerated conditions.