Similarity Factor F2 Research Articles

Finding Use for Sorghum Bicolor Leaf Sheath in Coating Technology

This study aimed to investigate the potential use of aqueous extract of Sorghum bicolor leaf sheath (SBLS) as a coating agent for paracetamol tablets. The mechanical properties of the coated tablets were assessed using crushing strength and friability test, while the release properties of the tablet were evaluated using disintegration and dissolution tests. The physicochemical properties of the coated tablets did not show any striking differences when compared with the uncoated tablet as par compendium specifications, which formed the basis for performing further in vitro dissolution study. Our data showed that SBLS enhanced the hardness and friability of the tablets in a dose-dependent manner. Tablets coated with 3, 5, and 7.5% of SBLS disintegrated in 8.13, 6.25, and 4.13 minutes, respectively, while the uncoated tablet disintegrated in 0.7 minutes. Furthermore, 3, 5, and 7.5% of SBLS-coated tablets exhibited slower release of their active ingredient (releasing 21, 16, and 17%, respectively) than that of the uncoated tablet (releasing 40%) in 5 minutes. Besides, comparison between the dissolution profiles was successfully achieved using difference factor (f1) and similarity factor (f2). The apparent dissimilarity between our coated tablets and the uncoated one led to further study of convolution in vitro–in vivo correlation, with the aim to obtain data that converted into mathematical prediction of in vivo data. For all batches, the percent predictable errors of C max and T max were within the acceptable limit of no more than 10%. In summary, SBLS aqueous extract is a potential and protective coat agent for paracetamol tablets. The in vitro established dissolution of the coated tablets provided scientific information for the prediction of the in vivo plasma drug profile.

Dissolution Profile Evaluation of Eight Brands of Metformin Hydrochloride Tablets Available in Jimma, Southwest Ethiopia.

BackgroundDissolution is the critical quality control parameter and used to predict an in vivo oral bioavailability, and it is used to support bio-waiver.AimTo evaluate and compare the dissolution profile of eight brands of metformin HCL 500 mg tablets available in Jimma town, Southwest Ethiopia.MethodsThe study was conducted in Jimma town, Ethiopia. Eight (seven brands and one comparator) metformin HCL 500 mg tablets were included. The dissolution study was conducted as per United States Pharmacopeia, and the dissolution profile was compared by one-way ANOVA, model-dependent and model-independent approaches.ResultsAll of the included tablet brands complied with single-point dissolution study specification. Statistical comparisons of the dissolution profile by one-way ANOVA revealed that all brands had similar dissolution profiles (p=0.89). All of the brands had a similarity factor (f2) >50% and the difference factor (f1) <15. The entire brands followed the Weibull curve approach (the highest coefficient of determination and lowest Akaike Information Criteria) for the release of an active pharmaceutical ingredient.ConclusionAll of the brands complied with single point dissolution study and all of them could be used interchangeably with the innovator drug. All brands followed the Weibull method for the release of the drug substance.

DESIGN OF CONTROLLED RELEASE MUCOADHESIVE BUCCAL TABLETS OF IVABRADINE HCL USING SINTERING TECHNIQUE

Objective: The objective of the present work was to study the use of the sintering technique, a relatively new concept in pharmaceutical sciences, in the development of mucoadhesive buccal tablets for ivabradine Hydrochloride.&#x0D; Methods: The method consisted of blending drug, hydroxypropyl methylcellulose (HPMC K100M), carnauba wax, and other excipients followed by direct compression into tablets. The compressed fluffy matrices were sintered at two different constant temperatures like 50 °C and 60 °C for two different periods like 1.5 h and 3 h in a hot air oven. The effect of sintering on tensile strength, dissolution profile, and other parameters were studied. The drug-polymer-excipient compatibility was evaluated by Fourier transform Infrared (FTIR) and differential scanning calorimetric (DSC) studies.&#x0D; Results: The sintering condition markedly affected the drug release properties, hardness, and friability of the tablets. Based on the f2 similarity factor value, Ex-vivo mucoadhesive strength, Ex-vivo residence time, and in vitro dissolution studies, formulation F3SD was selected as an optimized formulation. Drug release followed a non-Fickian diffusion mechanism with the Higuchi model release kinetics. Stability studies of mucoadhesive buccal tablets in normal human saliva indicated the stability of the drug and buccal tablet in the oral cavity. Stability studies as per ICH guidelines revealed that optimized formulation was stable on storage conditions.&#x0D; Conclusion: The sintering technique provides a significant and convenient method for the development of a controlled release dosage form that can be used in the design of mucoadhesive buccal tablets of Ivabradine HCL.

In vitro Bioequivalence Study of Five Generic Products and the Innovator Brand of Mebeverine Hydrochloride Extended- Release Capsules in Iran Market

Physicians tend to prescribe brand-name medicines for treating specific diseases. This might be due to the better clinical effects of these medicines compared to the generic ones. The aim of the present study was to evaluate in vitro bioequivalency between five generic products (T1, T2, T3, T4, T5) of mebeverine 200 mg extended-release capsules marketed in Iran and the innovator brand (Colofac® retard, Abbott Healthcare SAS, France). To evaluate the differences between generic products and the innovator brand, weight variation and dissolution analysis were performed. Acceptance value was calculated to investigate weight variation between different products. Dissimilarity factor (f1 ) and similarity factor (f2 ) were calculated to differentiate between the dissolution profile of the innovator brand and generic products. Innovator brand and all the generic formulations passed the United States Pharmacopoeia (USP) weight variation test. However, dissolution results indicated that among five generic formulations only T1, T4 and T5 were similar to the innovator brand but T2 and T3 did not pass USP requirements. Some pharmaceutical formulations may pass the pharmacopeia requirements but might show significant differences through in vitro equivalence studies. These differences could result in clinically diverse effects. Moreover, dissolution analysis seems to be a suitable procedure to detect these variations.

Industrial application of QbD and NIR chemometric models in quality improvement of immediate release tablets

Quality by Design (QbD) and chemometric models are different sides of the same coin. While QbD models utilize experimentally designed settings for optimization of some quality attributes, these settings can also be utilized for chemometric prediction of the same attributes. We aimed to synchronize optimization of comparative dissolution results of carvedilol immediate release tablets with chemometric prediction of dissolution profile and content uniformity of the product. As an industrial application, selection of variables for optimization was done by performing risk assessment utilizing the archived product records at the pharmaceutical site. Experimental tablets were produced with 20 different settings with the variables being contents of sucrose, sodium starch glycolate, lactose monohydrate, and avicel Ph 101. Contents of the excipients were modelled with F1 dissimilarity factor and F2 similarity factor in HCL, acetate, and USP dissolution media to determine the design space. We initiatively utilized Partial Least Square based Structural Equation Modelling (PLS-SEM) to explore how the excipients and their NIR records explained dissolution of the product. Finally, the optimized formula was utilized with varied content of carvedilol for chemometric prediction of the content uniformity.

Quality attributes of twenty-nine brands of ciprofloxacin: post-marketing in vitro analyses, microbiological assay and in vivo simulation

Ciprofloxacin is a fluoroquinolone antibiotic employed to treat infections. There are over three hundred registered generic brands of ciprofloxacin in Nigeria. There has been an observed marked variation in therapeutic or clinical outcome with change in brands by health professionals and patients. In a previous study of six (6) brands we had reported a high degree of inequivalence. In this study, twenty-nine (29) brands of ciprofloxacin were extensively evaluated against compendia requirements. Microbial sensitivity against two test organisms was conducted. In-vitro drug release and in-vivo simulation were established. Analysis of the data generated indicated that all brands passed qualitative test using TLC and disintegration test, six failed hardness test, one failed friability, nine failed antimicrobial assay and six failed percentage content assay. Conclusions drawn from the study for evidence-based clinical decisionwould include the fact that three brands only were found to be bioequivalent to the innovator brand, Ciproxin; while eight brands were bio-inequivalent using the three models of similarity factor (f2), and difference factor (f1) in two media and dissolution efficiency (DE) in pH 4.5. The three brands (Cipro-All, Cifran And Ciprogem) may confidently be used interchangeably with the innovator brand&#x0D; Keywords: Bioequivalence; Ciprofloxacin Drug quality; Generic substitution; Post-marketing surveillance

Development and characterization of lyophilized cefpodoxime proxetil-Pluronic® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity

The aim of this study was the development of hard-cellulose capsules containing cefpodoxime proxetil (CEF) (BCS Class II) loaded novel Pluronic® F127 (P127)/Polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) using ultrasonic probe induced solvent-lyophilization method for effective antibacterial treatment by means of improved saturated aqueous solubility, dissolution rate, reduced particle size, and wettability. SDs were evaluated for physical and solid-state analyses. The solubility of pure CEF was calculated as 0.269 ± 0.005 mg/mL, SDs formulated with P127/PVP exhibited increased solubility from 3.5- to 8-fold. Molecular distribution of CEF in SDs and formation of CEF loaded amorphous polymeric network were confirmed with morphological study, thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), and 1H-NMR studies. Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), and Klebsiella pneumoniae (ATCC 700603) were used to investigate the antibacterial effectiveness of the SDs. The minimum inhibitory concentration (MIC) values of the P127/PVP SDs were found 2–8 times lower than the pure CEF. All SDs from hard-cellulose capsules exhibited significantly faster release than unprocessed CEF. The profiles of SDs and reference were detected to be dissimilar according to difference (f1) and similarity factor (f2). Hard-cellulose capsules containing CEF loaded P127/PVP SDs appear to be feasible alternative to commercially available CEF tablets for effective antibacterial therapy at lowest dose.

Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies.

Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f2). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20–53 µm size containing 165.6 ± 3.6 µg Dx/mg MS) equivalent to 828 µg of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye.

Evaluation of Dissolution Profiles of a Newly Developed Solid Oral Immediate-Release Formula Containing Alpha-Lipoic Acid

Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f2 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f2 = 31.6); the optimal profile was obtained for Formula #4 (f2 = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations.

Preliminary Characterization and Comparison of Mucilage from Leaves of Hibiscus Sabdariffa L. as A Tablet Binder

The present research dealt with the extraction and characterization of mucilage from the Hibiscus sabdariffa leaves. Compared with normal binding agents such as starch and Poly Vinyl Pyrrolidine (PVP), the mucilage of Hibiscus sabdariffa (HSM) was assessed for its binding properties in tablet formulations. Tablets were formulated using HSM, starch and PVP as binders at a various concentration to evaluate its comparative binding efficiency. The compressed tablets were analyze for their quality control tests as per IP. The extracted HSM showed the characteristics of mucilage and good physicochemical properties. The FTIR and thermal analysis compatibility tests showed that there were no significant reactions between the drug and mucilage. Granule properties of various formulations were found to be comparable and have excellent flow characteristics. Post compression parameters suggested that tablets formulated with mucilage had better hardness and friability as that of the tablets prepared with starch and PVP. The formulations exhibited a better and more consistent release as compared to standard formulations using starch and PVP as a binder. The statistical analysis of in vitro dissolution profile by using DD solver software for difference factor (f1), similarity factor (f2), and Rescigno index (ξ) values also indicated promising results. The results notably indicate that binding property of HSM was at par with starch and PVP.

Investigation of Dry Granulation and Wet Granulation Effect on Dissolution Profile of the Developed Film Coated Tablets Containing Eplerenone

The objective is to observe and improve drug release of Eplerenone which is BCS Class II API by applying dry granulation and wet granulation process. Inspra 50 mg film coated tablets, manufactured by Pfizer, were taken as reference product to compare with dissolution profiles of dry granulation applied product and wet granulation applied product. Investigation of the effect of wet granulation process on dissolution profiles of Eplerenone 50 mg film coated tablets has been demonstrated out in the scope the study. While f2 similarity factor is 44.93 for dry granulation applied product, it is 60.62 for wet granulation applied product when compared to reference product. It comply that dissolution rate of wet granulation applied product is more proper to the specification than dry granulation applied product. The study demonstrates the effect of different granulation process on dissolution rate.

Optimization of Glipizide Floating Matrix Tablet Using Simplex Lattice Design

The aim of the present study was to prepare the floating matrix tablet of glipizide by applying Simplex lattice design using kappa carrageenan, Hydroxypropylmethylcellulose K15M and sodium bicarbonate as independent variable. The similarity factor (f2), time to release 50 % of drug and time to release 90 % of drug were taken as dependent factors. A total of 14 batches were prepared as given by Design-Expert® Software (version- 9.0.6, Stat-Ease) and the response obtained for the dependent variables was statistically evaluated. Radiological study was performed on healthy albino rabbits for checking the gastroretention for optimized floating tablet of glipizide. The results indicated that the formulation G-simplex lattice design 8 with 50 mg of Hydroxypropylmethylcellulose, 30 mg of kappa carrageenan and 10 mg of sodium alginate is the optimized formulation with highest desirability. The in vivo X-ray imaging study clearly revealed that the optimized formulations remained afloat in gastric fluid up to 12 h in the stomach of rabbit, which shows the possibility of the formulation to remain in the stomach of human being for the desired period. It was concluded that the simplex lattice design is suitable for efficiently optimizing the floating matrix tablet of glipizide.

Розробка та валідація ВЕРХ-МС методики визначення мемантину гідрохлориду для вивчення профілів розчинення

A method for quantitative determination of memantine hydrochloride by HPLC with mass spectrometric detection (HPLC-MS), suitable for the study of dissolution profiles of tablets "Mematon IС" was developed. Chromatographic determination was performed using a mobile phase of methanol - 0.1% (v/v) aqueous solution of formic acid (55:45) on a column of Zorbax Eclipse Plus C18 size 10 cm Ч 4.6 mm (3.5 μm) at a flow rate of 1 ml/min. The linearity interval in the appropriate dissolution media is 35 - 150 % of the normalized content of memantine hydrochloride in the tablet. The method is validated on the parameters of specificity, accuracy, correctness, linearity in the studied range of concentrations, robustness. The stability of the tested solutions and reference solutions in the case of their storage at room temperature for 24 hours was confirmed. It is established that in the case of the study of solutions prepared in a dissolution medium of 0.1 M hydrochloric acid solution pH 1.2, there is a need to preneutralize hydrochloric acid before analysis, because it, as stronger than formic acid, almost completely ionizes all dissolved molecules, which leads to a significant deviation of the linear dependence of the analytical signal on the concentration of the analyte. Neutralization is performed with 0.1 M sodium hydroxide solution, which is added to the sample of the test solution. The release of more than 85 % of memantine hydrochloride in 15 min in all dissolution media indicates the similarity of the dissolution profiles and does not require the calculation of the similarity factor f2.

Assessment of physicochemical properties and comparison of the dissolution profile of amoxicillin caplets

Background: Marketed drugs must meet the required standards to guarantee product quality. Amoxicillin is a generic compound marketed under various trademarks as copy drugs. Amoxicillin caplets are an immediate release dosage form of BCS class I. An essential aspect of evaluating copy drugs is to assess the equivalence for their treatment to the innovator drugs to ensure the safety and effectiveness of the circulating copy drugs. Objective: The study aims to evaluate the physicochemical properties and compare the dissolution profile of amoxicillin caplets available in the market. Methods: Five amoxicillin caplet products, four test products, and one reference product were tested for their physicochemical properties and dissolution. The dissolution test was carried out with a type II device at a speed of 75 rpm in 900 mL of media buffered at pH 1.2, 4.5, and 6.8 and at a temperature of 37 +/- 0.5degrees celcius. The dissolution profile was analyzed by comparing it with the similarity factor (f2) parameters. Results: Two of the four amoxicillin caplet products had a similar dissolution profile to the reference products, namely products A and B. Products C and D were dissimilar because f2 was lower than 50 at pH 4.5. The caplets tested had almost the same dimensions, and all caplets met the requirements for uniformity of content, hardness, disintegration time, and dissolution. Conclusion: Not all of the amoxicillin caplets in the market have a similar dissolution profile to the reference products. Keywords: caplets, amoxicillin, dissolution, similarity factor

&lt;p&gt;In vitro Comparative Quality Assessment of Different Brands of Furosemide Tablets Marketed in Northwest Ethiopia&lt;/p&gt;

BackgroundThe use of ineffective and poor quality drugs endangers therapeutic treatment and may lead to treatment failure. For desired therapeutic effect, drugs should contain the appropriate amount of active pharmaceutical ingredient and the required physical characteristics.AimThe aim of this study was to evaluate quality as well as physicochemical bioequivalence of different brands of furosemide tablets marketed in Bahir Dar, Northwest Ethiopia.MethodsFive different brands of furosemide tablets were purchased from community pharmacies in Bahir Dar city, Northwest Ethiopia. The quality control parameters of furosemide tablets were determined by identification, weight variation, disintegration, assay and dissolution tests and the results were compared with USP and BP pharmacopoeial standards. Difference (f1) and similarity (f2) factors were calculated to assess in vitro bioequivalence requirements.ResultsIdentification test results revealed that all samples contained the stated active pharmaceutical ingredients. The results of weight variation tests indicated that all samples complied with USP specification limits. The active pharmaceutical ingredients quantitative assay showed that all the brands of furosemide tablets were between the 90% and 105% limit of label claim. Similarly, all samples fulfilled disintegration time (i.e., ≤30 min) and dissolution tolerance limits (i.e., Q ≥80% at 60 min). Hence, none of the samples were found to be counterfeit and/or substandard. Difference factor (f1) values were <15 and similarity factor (f2) values were >50 for all the tested brands of furosemide tablets.ConclusionThis study revealed that all the furosemide brands met the quality specification of weight variation, hardness, friability, dissolution, disintegration and assay. The study also indicated similarity in the dissolution profile of the brands of furosemide tablets with the innovator product. Hence, all of these generic brands could be substituted with the innovator product in clinical practice.

Application of Dominance-Based Rough Set Approach for Optimization of Pellets Tableting Process.

Multiple-unit pellet systems (MUPS) offer many advantages over conventional solid dosage forms both for the manufacturers and patients. Coated pellets can be efficiently compressed into MUPS in classic tableting process and enable controlled release of active pharmaceutical ingredient (APIs). For patients MUPS are divisible without affecting drug release and convenient to swallow. However, maintaining API release profile during the compression process can be a challenge. The aim of this work was to explore and discover relationships between data describing: composition, properties, process parameters (condition attributes) and quality (decision attribute, expressed as similarity factor f2) of MUPS containing pellets with verapamil hydrochloride as API, by applying a dominance-based rough ret approach (DRSA) mathematical data mining technique. DRSA generated decision rules representing cause–effect relationships between condition attributes and decision attribute. Similar API release profiles from pellets before and after tableting can be ensured by proper polymer coating (Eudragit® NE, absence of ethyl cellulose), compression force higher than 6 kN, microcrystalline cellulose (Avicel® 102) as excipient and tablet hardness ≥42.4 N. DRSA can be useful for analysis of complex technological data. Decision rules with high values of confirmation measures can help technologist in optimal formulation development.

IN VITRO RELEASE PERFORMANCE OF METFORMIN HYDROCHLORIDE FORMULATIONS USING THE FLOW-THROUGH CELL METHOD

Objective: The objective of this work was to evaluate the in vitro release performance of metformin hydrochloride formulations (500-mg tablets) using the hydrodynamic environment of the flow-through cell method. Results were compared with those generated by the official dissolution test (USP basket apparatus).&#x0D; Methods: The reference drug product and three generic formulations were tested with phosphate buffer pH 6.8 as dissolution medium. Dissolution profiles were carried out with an automated flow-through cell apparatus using laminar flow at 16 ml/min. Drug was quantified at 233 nm during 45 min. Dissolution profiles were compared with the calculation of f2 similarity factor, mean dissolution time, dissolution efficiency, t50% and t63.2%. Dissolution data were adjusted to several mathematical models such as Makoid-Banakar, Peppas-Sahlin, Weibull and Logistic.&#x0D; Results: With the flow-through cell method and at 45 min less than 60% of metformin hydrochloride dissolved was found, while with the USP basket apparatus, less than 75% of the drug was found. Some generic formulations showed f2&gt;50 with both USP apparatuses, but statistical comparisons of parameters indicated significant differences between their dissolution profiles and reference. Due to variability obtained no dissolution profiles were compared by model-dependent approach.&#x0D; Conclusion: To demonstrate safe interchangeability between metformin hydrochloride generic formulations and reference bioequivalence studies should be performed. It is important post-marketing monitoring of the commercial formulations because health regulatory agencies of each country must ensure drug products with quality, safety, and efficacy at the lowest possible cost.

Application of Similarity Factor (f2) and Time Required to Drug Release (t%) Indicators for Dissolution Profiles Comparison of Paracetamol Tablets

Application of Similarity Factor (f2) and Time Required to Drug Release (t%) Indicators for Dissolution Profiles Comparison of Paracetamol Tablets

Impact of Tablet Shape on Drug Dissolution Rate Through Immediate Released Tablets.

Purpose: The aim of this study was to evaluate the influence of the geometric shape on the dissolution rate of the domperidone, a drug model for immediate release dosage form. In this regard, a lack of sufficient information about the effective dissolution rate of the drugs regarding their shapes has made this issue an interesting subject for researchers. Methods: For this purpose, three tablet shapes, namely flat and biconvex both in a round and oblong shapes, with different four sizes were modelled for the preparation of domperidone tablet. In vitro dissolution test was accomplished using a USP dissolution apparatus II. The drug dissolution rate was assessed by calculating various dissolution parameters; e.g., dissolution efficiency (DE), mean dissolution rate (MDR), mean dissolution time (MDT), and difference and similarity factors (f1 and f2 ). Results: Regarding the disintegration time, the larger tablets showed a faster disintegration time. When the size of the tablets was smaller, the amount of released drug was significantly decreased. In addition, #9 tablets with a flat or biconvex geometry had obvious effects on the DE values. Generally, biconvex tablets had higher DE percentage than the flat tablets. Conclusion: Noticeable differences in dissolution parameters by considering the different geometric shapes play an important role in the drug release kinetics which makes a significant effect on quick onset of action in oral administration.

Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach.

This study was focused on the formulation of the multi-unit extended-release peroral delivery device of lamotrigine for better management of epilepsy. The single-unit extended-release peroral preparations often suffer from all-or-none effect. A significant number of multi-unit delivery systems have been reported as a solution to this problem. But most of them are found to be composed of synthetic, semi-synthetic or their combination having physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation of multi-unit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing green manufacturing processes are being appreciated worldwide. Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing a simple green process and 23 full factorial design. The total polymer concentration, polymer ratio and [CaCl2] were considered as independent formulation variables with two different levels of each for the experiment-design. The extended-release beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinkerions provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software along with numerical optimization of the independent variables in order to meet USP-reference release profile. The optimized batch showed excellent outcomes with DEE of 84.7 ± 2.7 (%), CPR2h of 8.41± 2.96 (%), CPR5h of 36.8± 4.7 (%), CPR12h of 87.3 ± 3.64 (%) and f2 of 65.9. This approach of the development of multi-unit oral devices utilizing natural polysaccharides might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug products by the QbD route.