Traditional Oral Formulations Research Articles

Solubility of lamotrigine in age-specific biorelevant media that simulated the fasted- and fed-conditions of the gastric and intestinal environments in pediatrics and adults: implications for traditional, re-formulated, modified, and new oral formulations

BackgroundLamotrigine is an effective antiseizure medication that can be used in the management of focal and generalized epilepsies in pediatric patients. This study was conducted to quantify and compare the solubility of lamotrigine in age-specific biorelevant media that simulated the fasted and fed conditions of the gastric and intestinal environments in pediatrics and adults. Another aim was to predict how traditional, re-formulated, modified, and new oral formulations would behave in the gastric and intestinal environments across different age groups.MethodsSolubility studies of lamotrigine were conducted in 16 different age-specific biorelevant media over the pH range and temperature specified by the current biopharmaceutical classification system-based criteria. The age-specific biorelevant media simulated the environments in the stomach and proximal gastrointestinal tract in both fasted and fed conditions of adults and pediatric sub-populations. The solubility of lamotrigine was determined using a pre-validated HPLC-UV method.ResultsLamotrigine showed low solubility in the 16 age-specific biorelevant media as indicated by a dose number of > 1. There were significant age-specific variabilities in the solubility of lamotrigine in the different age-specific biorelevant media. Pediatric/adult solubility ratios of lamotrigine fell outside the 80-125% range in 6 (50.0%) and were borderline in 3 (25.0%) out of the 12 compared media. These ratios indicated that the solubility of lamotrigine showed considerable differences in 9 out of the 12 (75.0%) of the compared media.ConclusionFuture studies are still needed to generate more pediatric biopharmaceutical data to help understand the performances of oral dosage forms in pediatric sub-populations.

Formulation, optimization and in vitro evaluation of polymer-coated liposomes encapsulating nebivolol hydrochloride

Hypertension, also known as high blood pressure, is a serious medical condition that affects billions of people worldwide. Nebivolol hydrochloride, a β1–adrenergic blocking agent, is used by the oral route in the treatment of hypertension and congestive heart failure. However, its lipophilic nature and poor aqueous solubility restricts its oral bioavailability. To overcome limitations related with conventional oral formulations of the drug, uncoated and polymer–coated liposomes were developed and evaluated. Liposomes loaded with nebivolol hydrochloride were prepared by thin–film hydration method and characterized. The influence of chitosan or pluronic (F127) coating on the liposome properties was evaluated in terms of physicochemical characteristics, stability in simulated gastrointestinal fluids, mucin interaction, in vitro drug release and cytotoxicity studies. It was observed that coating the liposomes with either chitosan or pluronic affected the size, surface charge and encapsulation efficiency of the formulations. The surface morphology studies confirmed the vesicular shape of liposomes. The results obtained indicated that both polymer–coated liposome formulations maintained their stability in simulated gastrointestinal fluids and showed significant in vitro interaction with mucin. Polymer–coated liposome formulations showed much better cumulative release of the drug than uncoated liposomes. No aggregation was observed at the end of four–week storage period and low toxicity in Caco–2 cells was measured. The results demonstrated that polymer coating of liposomes could enhance the in vitro release of nebivolol hydrochloride and interaction with mucin following oral administration and might be attractive alternative nanocarriers to traditional oral formulations.

Current State and Opportunities with Long-acting Injectables: Industry Perspectives from the Innovation and Quality Consortium "Long-Acting Injectables" Working Group.

Long-acting injectable (LAI) formulations can provide several advantages over the more traditional oral formulation as drug product opportunities. LAI formulations can achieve sustained drug release for extended periods of time, which results in less frequent dosing requirements leading to higher patient adherence and more optimal therapeutic outcomes. This review article will provide an industry perspective on the development and associated challenges of long-acting injectable formulations. The LAIs described herein include polymer-based formulations, oil-based formulations, and crystalline drug suspensions. The review discusses manufacturing processes, including quality controls, considerations of the Active Pharmaceutical Ingredient (API), biopharmaceutical properties and clinical requirements pertaining to LAI technology selection, and characterization of LAIs through in vitro, in vivo and in silico approaches. Lastly, the article includes a discussion around the current lack of suitable compendial and biorelevant in vitro models for the evaluation of LAIs and its subsequent impact on LAI product development and approval.

Transdermal drug delivery system of domperidone sustained-release coated microsphere gels: In vitro characterization and in vivo evaluation

Domperidone (DMP) is an effective peripheral D2 dopamine receptor antagonist. It is commonly used in the treatment of nausea and vomiting caused by Parkinson's disease. An oral preparation, which is rapidly absorbed after administration, and reaches a peak plasma concentration within 15–30 min, is commonly used. However, owing to the “first-pass effect” of liver metabolism and intestinal wall metabolism, the oral bioavailability of domperidone is low, and the action period is long. Therefore, in the present study, spray drying and emulsion solvent evaporation were combined to prepare a coated microsphere preparation with sustained release effect, and a gel matrix was selected to prepare a sustained-release coated microsphere gel for transdermal drug delivery. The pharmacokinetic results showed that the transdermal sustained-release coated microsphere gel effectively increased the Tmax, Cmax, T1/2, and AUC compared with those of an oral DMP group (P < 0.05), and the relative bioavailability was 3.2 times that of the oral DMP group. This indicates that the preparation was able to ameliorate the problems associated with a traditional oral DMP formulation. Therefore, the present study may provide a theoretical basis for the transdermal delivery of DMP sustained-release microspheres.

Formulation and evaluation of colon targeted extended-release prednisolonematrix tablets

The prepared tablets met the compendia limits in termsof physiochemical parameters and dissolution studies. The mixture of 30 mg pectin and 30 mg of xanthan gum as matrix and 10% w/v of Eudragit RS100 solution as coating material werebest suitable in colon targeteddrug delivery system to provide optimum prednisolone release and protect it from SGF andSIF. As a result, colon delivery of prednisolone appeared to be apromising alternative to its traditional oral formulation.

Spray Dried Mucoadhesive Microparticles of Donepezil with Chitosan and Carbopol in Alzheimer’s Disease

Background: The traditional oral formulation for Alzheimer’s disease treatment has the drawbacks of first-pass metabolism, plasma protein binding, and poor blood-brain barrier penetration. This study was conducted to establish the nasal route of administration for donepezil formulations in Alzheimer’s disease. Materials and Methods: Donepezil mucoadhesive microparticles synthesized by spray-drying and evaluated for Infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The ex vivo study was done with Franz’s diffusion cell using goat nasal mucosa. The in vivo study was performed on the Albino rat’s nasal route for determining drug concentration by HPLC analysis in brain tissue at single-point evaluation. Results: The microparticles were with optimum size with no drug-polymer interaction in Infrared spectroscopy and Differential scanning calorimetry. Scanning electron microscopy exhibited morphology of spherical or ellipsoid microparticles with efficient drug entrapment. The percentage drug release for chitosan microparticles was 66.57 to 85.74 and for carbopol microparticles was 69.54 to 91.53 in the ex vivo permeability study. In vivo studies showed that drug concentrations of 110.48% to 114.92% for chitosan batches and 111.87% to 142.08% for carbopol batches were superior to controls. Conclusion: Ex vivo permeability study revealed drug release patterns with as high as 85.74% ±0.02 for DCH2 formulation and 91.53±0.3% for DC3 formulation. In in vivo study formulation DCH2 displayed drug concentration 110.87±6.87% and DC3 shown 129.51±9.82% over the control batch which is conclusive for improved drug delivery of donepezil through mucoadhesive microparticles for the nose to brain targeting in Alzheimer’s disease.

Different Methods of Preparation, Evaluation and Comparison of One Traditional Oral Liquid Formulation for Potential Antihyperlipidemic Activity in Hyperlipidemic Wistar Rats

Kashayam are unique Ayurvedic Formulation, most of them Polyherbal oral dosage form, used as a medicinal rationale. One of them Kokilaksha Kashayam, Quality of Kokilaksha Kashayam depends only on quality of starting materials, processing of ingredients, meticulous crushing, heating cycle.In traditional system of medicine like Ayurveda, Kokilaksha Kashayam is one of the traditional Indian medicine which is a polyherbal preparation treated with plant extract. It is generally used in the treatments of disorders related to Anti-inflammatory, Analgesic,heart, cancer etc. however detailed characterization studies after preparation &amp; comparison with marketed formulation are significant which can express authenticity of the product. Here the research work deals with the preparation of Kokilaksha Kashayam as per the procedure mentioned in the Ayurvedic text and modern method of preparation. Prepared Kokilaksha Kashayam was characterized and identified by different Analytical techniques, then evaluate preclinical pharmacological studies and also compared with Marketed formulations. Special steps concerned in the preparation of Kokilaksha Kashayam include Upakara (Preparation), Jaran (Heating &amp; Stirring), Shoshan (Purification), Dravyaguna parlksa (Pharmacological experiments), tulana parlksa (comparison Study) by traditional or conventional as well as modern methods of preparation. These products obtained from Jaran (Heating &amp; Stirring), Shoshan (Purification) by water extraction (Decoction process) and marketable sample were analyzed for quality control checks, the parameters mentioned in Ayurvedic texts as well as in modern techniques of evaluation, and pre-clinical pharmacological studies such as Assay of lipid per- oxidation, Hypolipidemic Activity etc were done to find out nature and form of the prepared formulation. Analyzed the in-vitro with in-vivo Anti-hyperlipidemic activity, bio-accessibility of Kokilaksha Kashayam were also determined. The Study reveals that the prepared Kokilaksha Kashayam-T and Kokilaksha Kashayam-M was shown the antioxidant activity was expanded in focus subordinate way. Kokilaksha Kashayam -T and Kokilaksha Kashayam-M repressed the ferrous sulfate prompted lipid per-oxidation in a measurements subordinate way and demonstrated inhibitory focus (IC50) esteem 166.173 and 170.284 µg/ml individually observed from graphical representation. By Oral Administration of Kokilaksha Kashayam-T and Kokilaksha Kashayam-M for nine weeks at the measurement of 2 ml/kg fundamentally decreased serum cholesterol, serum LDL and serum triglycerides while indicated critical ascent in serum HDL when contrasted with high fat eating routine encouraged control gathering. Marketed Kokilaksha Kashayam additionally demonstrated critical decline in serum cholesterol, serum LDL, serum triglycerides and indicated noteworthy ascent in serum HDL. Atorvastatin (1.2 mg/kg, p.o.) was utilized as standard antihyperlipidemic drug.The Study confirmed prepared two kinds of Kokilaksha Kashayam as Kokilaksha Kashayam-T and Kokilaksha Kashayam-M and Compared with Marketed Formulation indicated noteworthy decrease in atherogenic record when contrasted with high fat eating routine bolstered control amass which emphatically underpins antiatherosclerotic property of Kokilaksha Kashayam. Hence, it is concluded that Kokilaksha Kashayam can be very useful as cardiac disorder and extending the freshly prepared more active than Marketed formulation.

Herbal Recipes, Drug Indications and Sustainability Potential of Traditional Oral Liquid Formulations in Ogbomoso, Nigeria

Confirmation of identity, along with determination of the quality and purity of herbal drug is an important step towards ensuring its safety and efficacy. This study therefore sought to document the botanical constituents and drug indications of traditional oral liquid herbal formulations (TOLHFs) manufactured in Ogbomoso, Nigeria. It also examined the conservation status of the medicinal plants so used alongside the cultivation efforts being made by the drug manufacturers in order to provide information on whether continual exploitation of the plants for TOLHFs is sustainable. Through a questionnaire, 14 traditional herbal medical practitioners (THMPs)provided information on the recipes of their products, the sources of their raw material herbs, and types of health conditions treated or managed with the drugs. Sustainability potential of the drugs was quantified as relative percentage of the three choices of sources of raw material herbs available to the manufacturers in conjunction with the conservation status of the plant species as recorded by the International Union for Conservation of Nature (IUCN).Fifty-seven medicinal plant species (in 34 angiosperm families) were used to formulate 71 herbal recipes that are indicated for treating 14 different health conditions.

Evaluating Solubility of Celecoxib in Age-Appropriate Fasted- and Fed-State Gastric and Intestinal Biorelevant Media Representative of Adult and Pediatric Patients: Implications on Future Pediatric Biopharmaceutical Classification System.

Prediction of performance of traditional, reformulated, and novel oral formulations in adults and pediatrics is of great importance. This study was conducted to assess solubility of celecoxib in age-appropriate fasted- and fed-state gastric and intestinal biorelevant media, classify celecoxib into biopharmaceutical classification system (BCS), and assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. Solubility of celecoxib was assessed at 37°C in the pH range specified by the BCS-based criteria in 13 age-appropriate biorelevant media reflective of the gastric and proximal small intestinal environment in both fasted and fed states in adults and different pediatric subpopulations. A validated HPLC-UV method was used to quantify celecoxib. Experimental and computational molecular descriptors and in vivo pharmacokinetic data were used to assign the permeability class of celecoxib. Celecoxib belonged to BCS class 2. The pediatric to adult solubility ratios were outside the 80-125% boundaries in 3 and borderline in 1 biorelevant media. Significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Findings of this study indicated that the criteria used in the adult BCS might not be directly applied to pediatric subpopulations.

Gas and high performance thin layer chromatographic based-determination method for quantification of thymol in semisolid traditional dosage forms

The control and standardization process of herbal products is a critical point in preparation of those medicaments. In Traditional Persian Medicine (TPM) literature, out of all the different pharmaceutical dosage forms, Jawarish is a semisolid gastrointestinal dosage form with positive related effects. Jawarish-e-Khuzi, including Zataria multiflora, Lepidium sativum, Trachyspermum ammi, Terminalia chebula, ferrous sulfate, and also honey is one of the popular mentioned traditional oral formulations. However, there have been no noticeable and proven control and standardization for this formulation. In this study, Jawarish-e-Khuzi was prepared based on one of the pharmaceutical textbooks of Traditional Persian Medicine (TPM). Using gas chromatography/mass spectroscopy (GC/MS), the volatile composition of this formulation was analyzed. Subsequently, Gas chromatography/flame ionization detector (GC/FID) and High-Performance Thin-Layer Chromatography (HPTLC) techniques were employed to determine the main component. The GC/MS results showed thymol as the main constituent. In the content determination process via GC/FID, thymol was proved to be 0.02% of the whole preparation. The outcome of HPTLC method also corresponded with that of GC/FID. Based on the method validation parameters, both GC/FID and HPTLC methods are useful for the volatile content determination of semisolid dosage forms.

PREPARATION AND EVALUATION OF MICROEMULSION CONTAINING ANTIHYPERTENSIVE DRUG

Objective: The aim of the present study was to design novel drug delivery system containing ramipril microemulsion. Ramipril is an antihypertensive drug having very low aqueous solubility and bioavailability. Ramipril microemulsion could be used as a possible alternative to the traditional oral formulation to improve dissolution rate and hence its bioavailability with avoidance of the first-pass metabolism.Methods: The microemulsion existence region was determined by constructing pseudoternary phase diagram and prepared by using four components orange oil, tween 80 as a surfactant, propylene glycol as co-surfactant and distilled water as the aqueous phase. The water titration method was employed for its determination. All formulated microemulsion were subjected for visual inspection, centrifugation and stability test. The all stable formulations were selected for further study.The optimized microemulsion formulation B-9 was subjected for various evaluation parameters such as, visual inspection, stability studies, pH, viscosity measurements, electrical conductivity, content uniformity and dye solubility test.Results: Results revealed that construction of phase diagram and use of phase titration method was a suitable technique for the preparation of microemulsion as most of the formulations were transparent. It was found that the best microemulsion result was found for ratio 2:1. The results of stress tests conclude that the optimized formulation was both physically and chemically stable for 8 mo. Also, The Fourier transform infrared (FTIR) radiation measurement and Differential scanning calorimetry (DSC) of optimized formulation indicate the compatibility of ramipril with orange oil, surfactant-tween 80 and cosurfactant-propylene glycol. From electrical conductivity 0.283 σ and staining test the prepared optimized formulation B-9 was found to be o/w type of microemulsion. The optimized B-9 formulation showed good viscosity 13.52±0.01cps and pH 3.21±0.02 with highest drug content uniformity was found to be 84.98±0.02 %.Conclusion: In the present study a satisfactory attempt was made to formulate a novel o/w microemulsion of ramipril which improves the gastrointestinal absorption by raising its water solubility and hence oral bioavailability is also enhanced.

Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study

PurposeErythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL).Materials and methodsThe present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL.ResultsThere was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated.ConclusionIn cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.

OPTIMIZATION OF BACOSIDE A LOADED SNEDDS USING D-OPTIMAL MIXTURE DESIGN FOR ENHANCEMENT INSOLUBILITY AND BIOAVAILABILITY

&lt;p&gt;&lt;strong&gt;Objective&lt;/strong&gt;:&lt;strong&gt; &lt;/strong&gt;The objective of present study is to enhance solubility and bioavailability of poorly soluble &lt;em&gt;bacoside A&lt;/em&gt; present in &lt;em&gt;Bacopa monnieri&lt;/em&gt; extract using self nano emulsifying drug delivery system (SNEDDS) for the treatment of Alzheimer's disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Solubility of the drug was assessed in various oils (edible as well as synthetic oil), surfactant and co-surfactant by saturation solubility study. Pseudo-ternary phase diagram was used to obtain appropriate concentration ranges of components include oil, surfactant and co-surfactant.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From the result of saturated solubility study and phase diagram, oleic acid, tween 20 and ethanol was selected as oil, surfactant and co-surfactant. The D-Optimal mixture design was used to optimize the formulation on the basis of solubility of drug and dilution potential. &lt;em&gt;In vitro&lt;/em&gt; dissolution, study showed 89% of drug release from optimized SNEDDS formulation compared to untreated drug&lt;em&gt; &lt;/em&gt;extract with 24% of drug release in 60 min. Ex vivo diffusion study showed more than 90% of drug diffused from optimized SNEDDS formulation compared to pure extract.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In a nutshell, the developed SNEDDS formulation using the design of experimentation approach held great potential as a possible alternative to traditional oral formulations of poorly soluble &lt;em&gt;Bacoside A &lt;/em&gt;to improve solubility and bioavailability.&lt;/p&gt;

Potential Investigation of Peceol for formulation of Ezetimibe self nano emulsifyingDrug Delivery Systems

The present work was aimed at formulating and physicochemical characterization SNEDDS (self Nano emulsifying drug delivery system) of ezetimibe and evaluating its in vitro and in vivo potential. The solubility of both drugs was determined in excipient screening studies. Pseudoternary phase diagrams were used to evaluate the Nano emulsification existence area, composed of different surfactants, co surfactants, and oils at different surfactant to-cosurfactant (S/CoS) ratios, and the system exhibiting the largest percentage area of the self-Nano emulsifying region was selected and optimum oil ratio in the SNEDDS was selected by evaluating the clarity, precipitation and mean droplet size of the resultant Nanoemulsions. The release rate of ezetimibe was investigated using an in vitro dissolution test. In vitro dissolution studies showed that the SNEDDS composed of Peceol (20% wt/wt), Tween 80 (30% wt/wt), Ethanol (30% wt/wt), and ezetimibe (20% wt/wt) had higher initial dissolution rates for both drugs when compared with plain EZT. More importantly, EZT SNEDDS had a significantly increased dissolution profile in distilled water and pH 4.0 acetate buffer, implying enhanced bioavailability. The underlying mechanism of the loading capacity of EZT was elucidated by measurement of the zeta potential analysis. The results implied that EZT was located both in the Nanoemulsion core and the surfactant–cosurfactant layer. Comparative pharmacokinetic evaluation of EZT SNEDDS was investigated in terms of C max, tmax and AUC using rats. The SNEDDS formulation significantly increases pharmacokinetics parameter as compared with plain ezetimibe. The optimized formulation was then subjected to stability studies and was found to be stable over 6 months. Thus, the study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of ezetimibe to improve its bioavailability

Lacidipine self-nanoemulsifying drug delivery system for the enhancement of oral bioavailability.

Low bioavailability of Lacidipine (LD), an calcium channel blocker pose many challenges in the treatment of hypertension. The objective of this study was to formulate and characterize LD self-nanoemulsifying drug delivery systems (SNEDDS) to improve oral bioavailability of the drug. Formulations were evaluated for globule size, surface morphology, emulsification time, cloud point, drug content, in vitro dissolution, ex vivo permeation, stability and oral bioavailability studies. Captex 810D, TPGS, Tween-60, Transcutol P and PEG 400 was selected based on the solubility study results. The optimized SNEDDS readily gets nanoemulsified at 37 °C with droplet size of 41 nm when mixed with 200 times of its water. Transmission electron microscope photographs confirmed the spherical shape of the globules. In vitro dissolution of SNEDDS showed more than 80% of drug release within 15 min. The ex vivo permeation of LD from SNEDDS is 4.8- and 9-fold higher compared to pure drug in the absence and presence of verapamil respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of SNEDDS is 2.5 times higher than marketed tablet. The results suggest that, the SNEDDS formulation can be used as a possible alternative for the traditional oral formulations of LD to improve its oral bioavailability.

Optimization, ex vivo permeation, and stability study of lipid nanocarrier loaded gelatin capsules for treatment of intermittent claudication.

In this study, an optimized nanodispersible oral dosage form (containing a lactate ester) was developed for cilostazol (CZL). CZL is a phosphodiesterase inhibitor used for intermittent claudication. We aimed to improve the dissolution rate and absorption of CZL giving it a better chance of oral bioavailability, and to evaluate its stability on storage. Suitable compositions of nanoemulsion preconcentrate formulations were screened via solubility and compatibility tests. Response surface methodology and a desirability approach were applied to optimize preconcentrates containing minimum amount of surfactant mixture, maximum amount of lipid, and possessing the smallest globule size, with the highest emulsification and dissolution rates and minimum risk of drug precipitation. As part of the optimization process, the main effect, interaction effects and quadratic effects of amounts of lipid, and surfactant/co-surfactant ratio on % transmittance, globule size, emulsification time, drug precipitation, and drug release were investigated. The optimized formulation consisting of 28.9% butyl lactate, 28.9% Capryol®, 27.82% Solubilisant Gamma® 2429, and 14.18% Transcutol® possessing a globule size of 60 nm was mixed with Aerosil® 200. This gave uniform free flowing granules, which were characterized for surface and powder properties. The self-nanoemulsifying granules (SNEGs) filled into hard gelatin capsules showed two- and threefold increase in CZL released compared with conventional tablet and pure drug, respectively. The amount of drug permeated using non-everted sac technique from the SNEGs was twofold higher than that permeated from the tablet suspension. The shelf life was 526 days at 25°C. Our study illustrated that the developed SNEGs, with bioenhancing ingredients, held great potential as a superior alternative to traditional oral formulations of CZL.

In vitro characterization and pharmacodynamic evaluation of furosemide loaded self nano emulsifying drug delivery systems (SNEDDS)

Poor water solubility is one of the reasons for erratic absorption after oral administration of furosemide (FSM), an antihypertensive loop diuretic. Self nano emulsifying drug delivery system (SNEDDS) is a novel drug delivery system utilized to improve the water solubility, permeability and ultimately bioavailability. FSM solubility was determined in various vehicles oils, surfactants and co surfactants. Self emulsification region for the rational design of SNEDDS formulations were identified by pseudoternary diagrams. Developed formulations were characterized by zeta potential determination, droplet size analysis, dilution test, viscosity determination, in vitro dissolution studies and in vivo pharmacodynamic evaluation. A remarkable increase in dissolution was observed for the optimized SNEDDS when compared with the plain FSM and marketed formulation by in vitro dissolution studies. The pharmacological effect of FSM was improved by SNEDDS formulation as compared to plain FSM. The study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of FSM to improve its bioavailability.

Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride

The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (Cmax) and the area under the curve (AUC0→12 h) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.

Characterisation and evaluation of self-microemulsifying drug delivery system of Brucea javanica oil

A self-microemulsifying drug delivery system (SMEDDS) of Brucea javanica oil (BJO) was developed and evaluated for its oral absorption and bioavailability. Based on a solubility study and pseudo-ternary phase diagrams, the self-microemulsifying formulation composed of BJO, Cremorphor RH40, Plurol Oleique CC 497 and glycerol (30/42/20/8, % w/w) was prepared and characterised, including particle size, morphology, in vitro cytotoxicity and in vivo anti-tumour effects. The mean diameter of the final formulation was 41.5±3.5 nm. The BJO-loaded SMEDDS (BJOS) and the control preparation of BJO were administered orally to beagle dogs for pharmacokinetics and bioavailability studies. Oleic acid, which was considered as the main active and indicative component in BJO, was determined by gas chromatography. The cytotoxicity and anti-tumour effects of BJOS were evaluated in SMMC-7721 and BGC-823 cancer cell lines and sarcoma 180-bearing mice. The data showed that the oral relative bioavailability of commercial emulsion of BJO (BJOE) was 2.3-fold higher than that of BJO. Moreover, the IC50 value of BJOS group was nearly one-fourth compared to that of commercial BJOE. BJOS could significantly inhibit tumour growth via intra-gastric administration. The Letter illustrates that the developed SMEDDS formulation possessed great potential to be an alternative for traditional oral formulations of BJO.

Preparation and In Vivo Evaluation of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Containing Ezetimibe

Ezetimibe is a poorly water-soluble drug with varying bioavailability. The main objective of present work was to develop self nanoemulsifying drug delivery system (SNEDDS) for enhancing solubility and bioavailability of ezetimibe, which is widely used in treatment of homozygous familial hypercholesterolemia and homozygous sitosterolemia. The formulation of ezetimibe SNEDDS was optimized by simplex lattice design, multiple regression analysis and ternary contour plot. The optimal formulation of SNEDDS comprised of 7.058% oil (Oleic acid), 82.94% surfactant (Tween-80) and 10.0% co-surfactant (PEG-400). Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region. The average globule size of SNEDDS containing ezetimibe was about 90.63 nm when diluted with water. No significant variations in globule size and ezetimibe content in SNEDDS were observed over a period of 3 months at 40 ± 2° C/75 ± 5% RH and 25 ± 3° C (room temperature). In vitro diffusion studies showed remarkable increase in diffusion of drug. In vivo studies (in rats) showed significant increase in absorption of drug as compared to plain drug and marketed formulation. The data suggested use of SNEDDS to provide great potential as alternative to traditional oral formulations of ezetimibe. Keywords: Ezetimibe, Self nanoemulsifying drug delivery system (SNEDDS), Simplex lattice design, globule size, Hyperlipidemia, Oleic acid, Tween-80, Polyethylene glycol-400, Zeta potential, In vivo pharmacokinetic