Drug Release In Phosphate Buffer Research Articles

PREPARATION AND EVALUATION OF PROPRANOLOL HCL AND CARBAMAZEPINE RELEASE PROFILES FROM POLY(Є-CAPROLACTONE) MICROPARTICLE BLENDS SYSTEM

Objective: The goal of this research was to look into the physicochemical properties of poly(-caprolactone) microparticle blends that contained medicines of various solubilities (Propranolol HCl [Pro] and carbamazepine [CBZ]). Methods: W/O/W emulsion for Pro and O/W emulsion for CBZ were used to create microparticle blends. With dispersion time intervals (DTI) of 0 and 60 min, the Pro emulsion (W/O) and CBZ oil phase (O) were dispersed in an external aqueous phase (W). Scanning electron microscopy was used to examine the morphology of microparticle blends (SEM). Focused beam reflectance measurements were utilized to monitor the particle size mean of emulsion droplets/hardened microparticles (FBRM). In phosphate buffer (pH 7.4), encapsulation efficiency (EE) and in vitro drug release were also examined. Results: The final microparticle blends generated by solvent evaporation method were spherical and had two populations, according to the findings. The size of microparticle blends prepared with DTI 60 min and stirring duration 4 h was bigger than those prepared with DTI 0 min, according to FBRM data. In microparticle blends, encapsulation efficiency ranged from 62.05±3.74 percent to 66.38±4.16 percent for Pro and 70.56±4.62 percent to 73.85±4.11 percent for CBZ. After 28 d, drug release in phosphate buffer revealed that Pro release (33%) was shorter than CBZ release (60%) from microparticle blends with DTI 60 min. This was related to the interaction of the oil phase (CBZ) with hard particles from the primary emulsion (Pro), in which the oil phase occluded and covered surface structure of the harsh particles from the primary emulsion. Conclusion: Novel microparticle blends comprising drugs/medicines with varying solubilities (e. g. propranolol HCl and carbamazepine) have a lot of promise as controlled-release drug delivery systems. The physical properties of microparticle blends were impacted by the type of dispersion time interval used.

Preparation and evaluation of various formulation effects of the second emulsion on the shape and release profile of propranolol HCl from ethyl cellulose microparticle blends

AbstractThe objective of this study was to investigate and characterize incorporated propranolol HCl (Pro) within ethyl cellulose microparticle blends using the solvent evaporation method. The microparticle blends were prepared with a water‐in‐oil‐in‐water (W/O/W) solvent evaporation method and contained the same drug Propranolol HCl (Pro). The first Pro emulsion (W/O) and second Pro emulsion (W/O) were dispersed in an external aqueous phase, with a dispersion time interval (DTI) of 0 and 60 min. The morphology of the microparticle blends was characterized by SEM. The mean particle size, chord length distribution and chord count of the emulsion droplets/hardened microparticles were monitored by focused beam reflectance measurement (FBRM). The encapsulation efficiency and in vitro drug release in phosphate buffer (pH 7.4) were also investigated. The resulting microparticles were spherical, of two populations. The mean particle size of the microparticle blends ranged from 104.26 μm to 127.64 μm. The encapsulation efficiency was about 76.53% to 78.81% for propranolol HCl in the microparticle blends. FBRM studies showed that the size of the microparticle blends prepared by the W/O/W (Pro) method with DTI 60 min and stirring time 4 h was larger than that of the microparticle blends with DTI 0 min. In vitro drug release studies after 28 days showed that the propranolol HCl release from microparticle blends with DTI 60 min (54.05%) was slower than from microparticle blends with DTI 0 min (73.28%). Based on these data, there is an interaction of the second primary emulsion with hard particles from the first primary emulsion, whereby the second primary emulsion blocked and coated pores on the surface of hard particles from the first primary emulsion. These blocking and coating effects of the microparticles depended on the method and the DTI. In conclusion, novel microparticle blends containing drugs of the same solubility offer high potential for controlled release drug delivery systems. © 2022 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

APPLICATION OF 32 CENTRAL COMPOSITE DESIGN FOR THE FORMULATION OF RAPID SOLUBLE ORODISPERSIBLE FILM OF DIPYRIDAMOLE

Objective: The aim of this investigation is to formulate, design, optimize and to an evaluation of the rapid soluble orodispersible film (OTF) of dipyridamole (DPI) using the solvent casting method by 32 central composite designs. Methods: Statistical design was used to optimize the preliminary formulations by selecting independent variables such as a polymer (HPMC-E52V, X1) and plasticizer (PEG400, X2) concentration as film-forming polymer and as a plasticizer and the dependent variables such as the release of drug in percentage (Y1), time of disintegration (sec, Y2) and tensile strength (N/m2 Y3). Results: The content of the drug was resulted in the range of 95.05–101 %. The physical properties were found to be colorless and homogenously clear and smooth surface. The folding endurance shown as without any scratches with the pH ranges from 6.35 to 6.75 and the prepared film was not irritated to the oral mucosa. Conclusion: The prepared films showed an optimum time of disintegration that is 25 sec, 96.74% drug release in phosphate buffer of pH 6.8 at initial 5 min and 85.98 % ex-vivo permeation studies after 30 min.

Preparation and In Vitro Evaluation of Controlled-Release Matrices of Losartan Potassium Using Ethocel Grade 10 and Carbopol 934P NF as Rate-Controlling Polymers.

Controlled-release formulations are essential for those drugs that require fine tuning of their activity to increase the ratio between therapeutic vs. adverse effects. Losartan potassium is among those drugs whose adverse effects may somehow impair its purported benefits. Previous investigations have been carried out to ascertain the suitability of several polymers for being associated with losartan. This study is focused on the effects of Ethocel grade 10 and Carbopol 934P NF on losartan release. Flow and physical properties were assessed according to the protocols standardized by the pharmacopeia (USP-NF 29), and the drug release in phosphate buffer (pH = 6.8) was measured for 24 h. Data evidenced good to excellent flow and physical properties according to the drug/polymer ratio and the addition of co-excipients. The release rate in 24 h was found to be 63–69% to 79–82% without or with the addition of co-excipients, respectively, following zero-order kinetics. The results also suggest a significant difference with the release profile of a traditional release losartan formulation. The results suggest the suitability of Ethocel grade 10 and Carbopol 934P NF as components of a controlled-release losartan formulation.

Formulation and Characterization of Fast Dissolving films of Etoricoxib

Etoricoxib belongs to a class of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). Etoricoxib acts by reducing the pain and swelling (inflammation) in the joints and muscles of people older than 16 years of age and older patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gout. The present study was aimed to formulate fast dissolving oral films to enhance bioavailability, avoid presystemic metabolism and fast onset of action. The Preformulation studies such as Micromeritics, melting point, partition coefficients, UV spectroscopy, thin layer chromatography, loss on drying were carried out. The fast dissolving oral film was successfully fabricated by solvent casting method. Oral film was fabricated using PVA and PVP polymer. The prepared films were evaluated for Organoleptic evaluations, film weight, thickness, folding endurance, tensile strength, drug content uniformity of films, surface pH, disintegration time and in-vitro dissolution studies and SEM study. The formulation F8 has shown disintegration time of 22±1 seconds and is more promising, showed drug release in phosphate buffer 6.8 pH 86.33% in 10 min. Hence formulation F8 was selected as best formulation. In the stability testing all films stored at elevated temperature showed slight change in pH, other parameters were found to be unchanged.

Formulation and development of Serratiopeptidase enteric coated tablets and analytical method validation by UV Spectroscopy.

Serratiopeptidase (SRP) is a proteolytic enzyme that emerged as one of the most potent anti-inflammatory and analgesic drugs. The purpose of the present study was to formulate and evaluate enteric-coated tablets for SRP and investigate their stability using a simple and validated analytical method by ultraviolet (UV) spectroscopy. The colloidal silicon dioxide (2.50%), sodium starch glycolate (3.44%), and crospovidone (2.50%) were used as appropriate excipients for the development of core part of tablets. To protect the prepared tablets from acidic environment in the stomach, white shellac, castor oil, HPMC phthalate 40, and ethyl cellulose were used. The seal coating and enteric coating attained were 2.75% and 6.74%, respectively. SRP was found to be linear at 265 nm in the concentration range of 25–150 µg/mL. The results revealed that our developed method was linear (R2 = 0.999), precise (RSD % = 0.133), and accurate (% recovery = 99.96–103.34). The formulated SRP tablets were found to be stable under accelerated conditions as well as under room temperature for 6 months (assay %: >97.5%). The in vitro drug release study demonstrated that enteric-coated tablets were able to restrict SRP release in both acidic environments: 0.1 N HCl and simulated gastric fluid (pH 1.2). Moreover, at 60 minutes, the formulated SRP tablets revealed 13.0% and 8.98% higher drug release in phosphate buffer (pH 6.8) and simulated intestinal fluid (pH 6.8), respectively, compared to the marketed tablet formulation. This study concludes that enteric-coated tablets of SRP with higher drug release in the intestine can be prepared and examined for their stability using validated analytical technique of UV spectroscopy.

Anti-Aβ-scFv-loaded polymeric nano-micelles with enhanced plasma stability.

Immunotherapy using recombinant monoclonal antibodies specifically Anti-amyloid-beta (Anti-Aβ) scFv is envisaged as an appropriate therapeutic for Alzheimer through reduction of amyloid-beta aggregation. The solubilization of therapeutics using polymeric micelles facilitates an improved bioavailability and extended blood half-life. In this study, the optimum production condition for Anti-amyloid-beta (Anti-Aβ) scFv was obtained. To increase the stability of plasma, Anti-Aβ-loaded polymeric micelles were synthesized. Escherichia coli SHuffle expression strain was used and purified by Ni-NTA. Pluronics P85 and F127 micelles were used for the Anti-Aβ delivery and were characterized in terms of morphology, drug loading and drug release in phosphate buffer and artificial cerebrospinal fluid. The stability profile was quantified at 4°C over a 30 days storage period. The stability in human plasma was also evaluated. Proteins expressed in SHuffle resulted in increased levels of protein expression and solubility. Low critical micelle concentration value and high micelle encapsulation efficiency (<200 nm) achieved via direct dissolution method. Anti-Aβ-loaded micelles were around 2.2-fold more stable than Anti-Aβ in plasma solution. A sustained in-vitro release of Anti-Aβ from micelles was observed. Results confirmed that Pluronic-micelles pose benefits as a nano-carrier to increase the stability of Anti-Aβ scFvin in the plasma.

Nose to brain delivery of Rotigotine loaded solid lipid nanoparticles: Quality by design based optimization and characterization

Rotigotine (RTG), for the treatment of Parkinson disease has low oral bioavailability (1–5%) due to its high gut clearance and restricted entry by brain barriers.RTG is dopamine (D1-D5) &5HT1A agonist and α-2 adrenergic receptors antagonist. In present research, RTG loaded Solid Lipid Nanoparticles (RTG-SLNs) was optimized to improve bioavailability via. nose to brain delivery. Quality by Design approach for the product development was used. Dynasan 118 as solid lipid and tween 80 as surfactant were optimized. RTG-SLNs were prepared by hot melt emulsification method using high speed homogenizer. Amongst various independent variables, critical variables were selected using 25−2 Fractional Factorial Design. Further optimization was done using central composite design. Design results were analyzed using ANOVA, Pareto chart, surface plots and desirability. Optimized RTG-SLNs gave desired particle size (129 nm), % Entrapment Efficiency (83%), Polydispersivity index (0.285), zeta potential (−23.1) and in-vitro drug release in phosphate buffer 7.4 for 30 h (99%). Further optimized batch was characterized using FTIR, TEM and AFM. From the ex-vivo permeability, cellular uptake study (confocal laser scanning microscopy) and histopathology study, RTG-SLNs was found permeable through goat nasal mucosa and non-toxic. Formulation was found stable during 3 months’ stability studies at refrigerated condition.

Nanofibrous Polydioxanone Depots for Prolonged Intraperitoneal Paclitaxel Delivery.

Prolonged chemodrug delivery to the tumor site is a prerequisite to maintaining its localised therapeutic concentrations for effective treatment of malignant solid tumors. The current study aims to develop implantable polymeric depots through conventional electrospinning for sustained drug delivery, specifically to the peritoneum. Non-woven electrospun mats were fabricated by simple electrospinning of Polydioxanone solution loaded with the chemodrug, Paclitaxel. The implants were subjected to the analysis of morphology, mechanical properties, degradation and drug release in phosphate buffer and patient-derived peritoneal drain fluid samples. In vivo studies were conducted by surgical knotting of these implants to the peritoneal wall of healthy mice. Non-woven electrospun mats with a thickness of 0.65±0.07 mm, weighing ~ 20 mg were fabricated by electrospinning 15 w/v% polymer loaded with 10 w/w% drug. These implants possessing good mechanical integrity showed a drug entrapment efficiency of 87.82±2.54 %. In vitro drug release studies in phosphate buffer showed a sustained profile for ~4 weeks with a burst of 10 % of total drug content, whereas this amounted to >60% in patient samples. Mice implanted with these depots remained healthy during the study period. The biphasic drug release profile obtained in vivo showed a slow trend, with peritoneal lavage and tissues retaining good drug concentrations for a sustained period. The results indicate that non-woven electrospun mats developed from biodegradable Polydioxanone polymer can serve as ideal candidates for easily implantable drug depots to address the challenges of peritoneal metastasis in ovarian cancer.

A smart gelatin nanoparticle for delivery of metoprolol succinate: A strategy for enhancing the therapeutic efficacy by improving bioavailability

The purpose of this study was to develop and evaluate of gelatin nanoparticles (GNPs) by nanoprecipitation method to increase metoprolol succinate (MES) peroral bioavailability. Prepared GNPs were evaluated in terms of its properties such as particle size, zeta potential, entrapment efficiency, drug loading, in vitro drug release, morphologyand in-vivo pharmacokinetic studies. The GNPs showed sustain drug release in phosphate buffer (pH 7.4) while less release in the 0.1 N HCl as compared to plain MES. The in vivo pharmacokinetics study on rabbits showed a rise in the bioavailability of the GNPs by 2.27 folds as compared to marketed formulation. FTIR studies performed on the GNPs indicated no drug-polymer interaction. Nanoparticles (NPs) prepared by nanoprecipitation method were found to be clear (through SEM) and their mean particle size was in the range of 59.83±0.14 to156.41±0.19 nm. The F-3 formulation exhibited the highest entrapment of 98.07±0.53. Zeta potential of all GNPs was in the range of 11.66 to 14.50 mV which indicates that they are moderately stable. Release study revealed that GNPs release drug at a sustained rate which assists in the absorption of MES through the blood. Further, in vivo studies induced in increased bioavailability of the MES which established the potential of developed carrier systems. Thus, it can be concluded that these prepared NPs might be one of the best preparation for the delivery of MES for better therapeutic efficacy.

Pullulan based oral thin film formulation of zolmitriptan: Development and optimization using factorial design

The goal of study was to formulate and characterize pullulan based oral thin film (OTF) of zolmitriptan by solvent casting method. Based on preliminary trials, glass, PEG 400 and sucralose were selected as casting surface, water-miscible plasticizer and sweetener for OTF, respectively. A 32 factorial design was used to study the effect of amount of PEG 400 (X1) and sucralose (X2) as independent variables on tensile strength (Y1), elasticity (Y2), % in-vitro drug release in phosphate buffer of pH 6.8 at 5min (Q5min, Y3) and overall taste of OTF (Y4) as responses. OTF of batch F4 (PEG 400, 200mg; sucralose, 12mg) was identified as an optimized batch showing in-vitro, in-vivo disintegration time 20.70 and 21.58s, respectively; 95.53% Q5min; satisfactory thickness, strength, % elongation, ease of handling, smooth mouthfeel, excellent overall taste; even distribution of all ingredients in pullulan OTF (SEM study); and stable film at specified conditions concluding that pullulan, PEG 400 and sucralose are used in combination to make palatable, stable OTF of zolmitriptan.

Formulation of Herbal Capsule Containing Trigonella Foenum-Graecum Seed Extract for the Treatment of Diabetes

Background: Trigonella foenum-graecum (fenugreek) seeds are reported to contain multiple antidiabetic constituents and hence widely used for the treatment of diabetes mellitus. The present investigation was aimed to formulate capsule formulations containing crude extract of fenugreek seeds in order to obtain antidiabetic formulations with more effective oral hypoglycemic activity, less side effects, increased patient compliance thereby providing multifaceted benefits. Methodology: Capsule formulations were prepared by encapsulation of granules prepared from the fenugreek seed extract with various concentration of sodium starch glycolate as superdisintegrant (0- 5%). Finished capsule formulations were evaluated for weight variation, disintegration time, drug content ( trigonelline ) content, in vitro -drug release, in vivo antidiabetic activity studies. Results: Fenugreek capsule formulations pass the test for weight since the percentage deviation of individual weight of capsule from mean were found within ±7.5%. Drug ( trigonelline ) content of all the formulations were more than 85%. Disintegration time ranged from 7-15 mins. Dissolution profile showed 77.06 - 90% drug release in phosphate buffer of pH 6.8 after 6 hours. Antidiabetic activity studies of capsules significantly ( p ≤ 0.001) reduced blood glucose level in diabetic rats after 15 days of treatment when compared to diabetic control group. Conclusion: From the results, we concluded that formulation of fenugreek seed extracts into suitable and appropriate herbal dosage form may be more desirable, advantageous and therapeutically more beneficial than incorporating the direct plant materials for the treatment of diabetes. Key words: Diabetes Mellitus, Fenugreek, Trigonelline , Capsule, Superdisintegrants.

Nimodipine-Loaded Pluronic® Block Copolymer Micelles: Preparation, Characterization, In-vitro and In-vivo Studies.

Nimodipine (NM), as a lipophilic calcium channel blocker indicated for the prevention and treatment of neurological disorders, suffers from an extensive first pass metabolism, resulting in low oral bioavailability. Polymeric micelles, self-assembled from amphiphilic polymers, have a core-shell structure which makes them unique nano-carriers with excellent performance as drug delivery. This investigation was aimed to develop NM-loaded polymeric micelles and evaluate their potential to cross the blood brain barrier (BBB). Micelles from Pluronics®P85, F127 and F68 were fabricated for the delivery of NM, using thin film hydration and direct dissolution techniques. Critical micelle concentration of the drug-free micelles was determined by pyrene fluorescence spectroscopy. Dynamic light scattering showed that in most cases, micelles less than 100 nm and low polydispersity indices were successfully developed. Transmission electron microscopy demonstrated spherical shape of micelles. The NM-loaded micelles were also characterized for particle size, morphology, entrapment efficiency, drug loading , in vitro drug release in phosphate buffer and artificial cerebrospinal fluid (CSF). Stability was assessed from size analysis, clarity of dispersion on standing and EE(%), following 3 months storage at room temperature. The in-vitro release of NM from polymeric micelles presented the sustained-release profile. Animal studies revealed the existence of fluorescein 5-isothiocyanate-labeled micelles in rat CSF following intraperitoneal administration, proving that the micelles crossed the BBB. Anticonvulsant effect of NM was shown to be significantly greater than that of NM solution. Our results confirmed that Pluronic micelles might serve as a potential nanocarrier to improve the activity of NM in brain.

Design, development and in-vitro evaluation of diclofenac taste-masked orodispersible tablet formulations

Context: Fast onset of action is prerequisite for acute pain medication. A palatable orodispersible medicine of diclofenac providing rapid analgesic effect should improve patient compliance and treatment.Objective: In the present study, diclofenac taste-masked orodispersible tablets (ODTs) with fast release characteristics were developed. Different taste-masking approaches and formulation concepts were screened in vitro for candidate selection.Materials and methods: Diclofenac was used as free acid. Five taste-masked microgranule formulations were prepared by wet granulation and/or coating processes, and compressed to ODTs. Citric acid (pH-modifying agent) and Eudragit® E PO (amino methacrylate copolymer) were used as taste-masking agents. Evaluation criteria were (i) disintegration time, (ii) processability and (iii) in-vitro dissolution profiles in simulated saliva (pH 7.4, 5 mL, 3 min) and compendial pH-change media (paddle, 50 rpm). The prototypes were compared to reference ODTs (without taste-masking). Most suitable ODT prototypes were selected and further evaluated for taste-masking efficiency using an electronic tongue.Results and discussion: In simulated saliva, the drug was slower released from the prototypes (between 1.1% and 15.5%) than from reference ODTs (23.7%). Less dissolved particles are thus expected in vivo for taste perception. Two ODT prototypes showed fast and complete drug release in phosphate buffer. The formulation providing the most efficient taste-masking was selected guided by electronic tongue data.Conclusion: A novel palatable and fast acting diclofenac ODT formulation was successfully developed. Formulation design, development and in-vitro evaluation used in this study may serve as rational approach for manufacturing taste-masked orodispersible dosage forms.

English

This study was designed for concealing the bitter taste of an anti-malarial drug, artemether, by using various coating substances. Four granular formulations (formulations A, B, C and D) of artemether were prepared using different excipients and then were coated using methocil&trade; E5 and opadry&reg;&nbsp;enteric solutions in a simple coating pan. In the initial 2 min, the cumulative percentage amount of drug release in phosphate buffer at pH 6.8 from pure artemether and formulation A, B, C and D was 59.4 &plusmn; 4.2, 55.7 &plusmn; 3.5, 48.2 &plusmn; 3.8, 43.4 &plusmn; 4.1 and 30.8 &plusmn; 3.7, respectively. Formulation D exhibited minimum bitterness as its taste masking efficacy (44.73 &plusmn; 4.98) was significantly (P &lt; 0.05) greater than other formulations. It can be concluded from results that granules of formulation D prepared by sodium metabisulphite and methyl paraben sodium and coated by opadry&reg;&nbsp;enteric had maximally reduced the bitterness of artemether with suitable dissolution behavior. &nbsp; Key words:&nbsp;Artemether, dry suspension,&nbsp;in vitro&nbsp;test, taste analysis.

Al3+ ion cross-linked interpenetrating polymeric network microbeads from tailored natural polysaccharides

Interpenetrating network (IPN) microbeads of sodium carboxymethyl locust bean gum (SCMLBG) and sodium carboxymethyl cellulose (SCMC) containing diclofenac sodium (DS), a non steroidal anti-inflammatory drug were prepared by single water-in-water (w/w) emulsion gelation process using AlCl3 as cross-linking agent in a complete aqueous environment. The influence of different variables like total polymer concentration, gelation time and crosslinker content on in vitro physico-chemical characteristics and drug release rate in different media was investigated. Drug loaded microbeads were evaluated through Fourier transform infra-red (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses. Scanning electron microscopy (SEM) micrograph of the beads suggested the formation of spherical particles. FTIR analysis indicated the stable nature of the drug in the blend microbeads. DSC and XRD analysis revealed amorphous state of drug after encapsulation. The drug release profile in acidic medium was considerably less in comparison to alkaline media. Formulations showed non-Fickian type transport mechanism. These tri-valent ion crosslinked beads not only improve drug encapsulation efficiency but also enhance drug release in phosphate buffer.

Chemico-physical investigation of tenofovir loaded polymeric nanoparticles

Tenofovir (PMPA), an acyclic nucleoside phosphonate analog, is one of the most important drugs used for the HIV treatment. Unfortunately, several adverse reactions are related to its i.v. administration owing to the saturation of an anionic renal transporter. In order to improve the drug administration, the PMPA was embedded into a new type of nanocarriers based on poly-(D,L-lactide-co-glycolide) (PLGA) and/or chitosan (CH). The strategies for the preparation of nanoparticles (Nps) with a more efficient drug loading respect to the one reported in the literature for PMPA nanoencapsulation were investigated. CH was added in the first inner emulsion or in the external phase during the second emulsion of water/oil/water (W/O/W) Nps. The addition of CH in the first inner emulsion was the most promising technique. The Nps have a Z-average of 230 nm, a Z-potential of -3 mV and an EE% of 15 that was 2.5-3 times higher than that obtained with PLGA Nps or CH Nps. In vitro release studies showed a limited control on drug release in phosphate buffer (pH 7.4) while an initial burst effect followed by a slow drug release was observed in acidic receiving phase (pH 4.6). These results suggest the PLGA/CH Nps should be an effective and attractive anti-HIV drug carrier to study the cellular uptake and drug delivery on target cells such as macrophages.

Preparation and characterization of metformin hydrochloride loaded-Eudragit®RSPO and Eudragit®RSPO/PLGA nanoparticles

The aim of the present study was to develop and characterize metformin HCl-loaded nanoparticle formulations. Nanoparticles were prepared by the nanoprecipitation method using both a single polymer (Eudragit®RSPO) and a polymer mixture (Eudragit/PLGA). The mean particle size ranged from 268.8 to 288 nm and the nanoparticle surface was positively charged (9.72 to 10.1 mV). The highest encapsulation efficiency was observed when Eudragit®RSPO was used. All formulations showed highly reproducible drug release profiles and the in vitro drug release in phosphate buffer (pH = 6.8) ranged from 92 to 100% in 12 h. These results suggest that Eudragit®RSPO or Eudragit/PLGA nanoparticles might represent a promising sustained-release oral formulation for metformin HCl, reducing the necessity of repeated administrations of high doses to maintain effective plasma concentrations, and thus, increasing patient compliance and reducing the incidence of side-effects.

Design and Development of Metformin HCl Floating Microcapsules using Two Polymers of Different Permeability Characteristics

The objective of the present investigation was to design a sustained release floating microcapsules of Metformin HCl using two polymers of different permeability characteristics Cellulose acetate butyrate (MW of 16,000) and Eudragit RL100 (MW of 150,000) using the oil-in-oil emulsion solvent evaporation method. Polymers were used separately and in combination (1:1) to prepare different microcapsules using acetone as organic phase. In all batches of microcapsules, the total polymer concentration was kept constant (10%w/w). No significant differences in drug loading in microcapsules made from different polymer were noted. Drug loaded microcapsules were found to float on 0.1M HCl for more than 8 hour. FT-IR study showed no drug polymer interaction. SEM study clearly revealed the smoothness of the spherically shaped particles. All the prepared microcapsules showed higher amount of drug release in phosphate buffer (pH 6.8) as compared to the release in 0.1M HCl (pH 1.2). Evaluation of the release data reveals that microcapsules prepared from RL100, Cellulose acetate butyrate and combination of both the polymers exhibit Higuchi spherical matrix release, followed by first order and zero-order release kinetics. Finally, the drug loaded floating microcapsules were found to be safe, economical and will overcome the drawbacks associated with the drug in conventional tablet form, by reducing plasma drug fluctuations.

Exploration of cold extrusion for the preparation of enteric minitablets of isoniazid

The objective of the present work was to formulate the enteric minitablets of isoniazid by cold extrusion method. The minitablets were prepared using isoniazid, hydroxylpropylmethylcellulose phthalate and dibasic calcium phosphate. The minitablets were coated using hydroxypropylmethylcellulose phthalate. Full factorial design was adopted to optimize the formulation. The minitablets showed good flow and acceptable friability. The drug release was resisted in 0.1 N HCl for 2 h from the optimized batch. The optimized batch showed more than 90% of drug release in phosphate buffer in 15 min. Capsules containing rifampicin powder and enteric isoniazid minitablets showed complete drug release in acidic and alkaline media respectively. The process of cold extrusion appears to be an attractive alternative to by-pass the existing patents.