pH Of Dissolution Medium Research Articles

Impact of dissolution medium pH and ionization state of the drug on the release performance of amorphous solid dispersions

Amorphous solid dispersions (ASDs) are widely employed as a strategy to improve oral bioavailability of poorly water soluble compounds. Typically, optimal dissolution performance from a polyvinylpyrrolidone vinyl acetate (PVPVA) based ASD is observed at relatively low drug loading limit. Above a certain drug load, termed limit of congruency (LoC), the release from ASDs significantly decreases. So far, the majority of the dissolution behavior has been tested in conditions where the drug primarily exists in unionized form. In this work, the impact of pH of the dissolution environment on the release performance of ASDs of an ionizable drug was studied. Atazanavir (ATZ), a weakly basic drug with a pKa of 4.5 was used as a model compound and PVPVA was used as a non-ionizable matrix polymer. Dissolution rate was measured using Wood's apparatus which normalizes the surface area of the dissolving tablet. The pH of the dissolution media was varied between 1 and 6.8, cover a range where ATZ exists as >99% ionized or unionized species. At pH 6.8, near complete release was observed only when the drug load was ≤ 6%. Unlike typically observed drastic decline in release behavior for PVPVA based ASDs above LoC, ATZ ASDs underwent gradual decline in dissolution behavior when the DL was increased to 8%. This was attributed to potential formation of an ATZ-PVPVA associated phase with dissolution rate slower than neat PVPVA. However, the 10% DL ASD showed negligible ATZ release. On another extreme (pH 1) where ATZ is ∼100% ionized, the dissolution rate of ATZ was faster than that of PVPVA. ASD dissolution rate was found to be slower than that of the neat drug but faster than PVPVA and interestingly, did not change with DL. This can be attributed to formation of an ionized ATZ-PVPVA phase which controls the dissolution rate of the ASD. At pH 3, where the drug is ∼97% ionized, near complete release was observed for drug loads ≤ 8%. To observe significant increase in drug loading with near complete release, >98% ionization of ATZ was required. At pH 2 where ATZ is ∼99.7% ionized, near complete release was observed for drug loads up to 30%. Furthermore, the deterioration in dissolution performance with an increase in drug load continued to be gradual at pH 2. The enhancement in dissolution performance did not correlate with solubility enhancement of ATZ due to ionization. We theorize that the enhancement in the dissolution performance due to ionization is the result of formation of an ionized ATZ-PVPVA phase which increases the hydrophilicity and the miscibility of the ASD. This can help resist water induced phase separation during ASD dissolution and therefore, result in continuous, and congruent dissolution of the drug and polymer.

Application of co-precipitated glutinous rice starch as a multifunctional excipient in direct compression tablets

Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.

UPLC-MS-based Method Development, Validation, and Optimization of Dissolution Using Quality by Design Approach for Low Dose Digoxin: A Novel Strategy

Background: Digoxin, a cardiac glycoside is the one of the most significant drugs of choice for the congestive heart failure treatment. As Digoxin is a BCS class IV drug, the dissolution is a critical quality attribute for its tablet formulation. Methods: Current work aims to quantify the dissolution drug release for low dosage digoxin of 0.0625mg tablets with targeted drug release of more than 80% at 60 minutes by highly sensitive, fast, and versatile UPLC-MS technique. UPLC-MS method operated by positive ionization mode with ACQUITY UPLC C18 (2.1 cm x 100 mm, 1.8 µm) column and flow rate of 0.3ml/min has been developed and validated for parameters like linearity, precision, accuracy, ruggedness, limit of detection (LOD) and limit of quantification (LOQ) as per the ICH guidelines. Results: LOD was found to be 21 ng/mL. Collision energy for digoxin was observed as 35eV for QDa mass detector along with 803.5m/z precursor ion and 651m/z daughter ion. An optimal custom experimental design was employed to optimize the final dissolution conditions. The critical dissolution factors selected for optimization were pH of dissolution media, dissolution media volume, rpm (rotations per minute). The %drug release (DR) was selected as a critical quality attribute with the desired response of drug release >80% at 60minutes. Outcomes of the design were further evaluated by statistical tools including ANOVA. The final optimized dissolution method consists of 500mL of pH 7.4 buffer with a USP apparatus of I (Basket) rotating at 120 rpm. Conclusion: In this current work, we have optimized the dissolution conditions by QbD, and developed a sensitive UPLC-MS method for quantification of digoxin, that can be used in routine quality control purposes efficiently in dissolution testing and quantification of batches of low dose digoxin tablets.

The Effect of Humidity on the Dissolution Kinetics and Tablet Properties of Immediate-Release Tablet Formulation Containing Lamotrigine.

This study aims to find the effects of high (75%) and low (30%) humidity conditions and its correlation with formulation composition on dissolution kinetics of lamotrigine (LMT) from prepared immediate-release tablets during one- and four-week periods. Two types of fillers microcrystalline cellulose (MCC) or anhydrous lactose (LAC), disintegrant sodium starch glycolate (NaSG, 0.5% or 4%), and lubricant magnesium stearate (MgST, 0.25% or 5%) were used. A three-factor two-stage complete factorial design (23) was used to assess the influence of the composition of the tested formulations. The tablets were produced by direct compression and characterized using a disintegration test, a resistance to crushing test, and dissolution tests (pH 1.2 and pH 6.8). Using Design Expert software, it was concluded that in addition to the effect of fillers on pH 6.8, NaSG has a significant impact after exposure to high and low humidity, as well as its interaction with LAC and MCC. In the dissolution medium pH 1.2, under conditions of high humidity, the content of MgST and NaSG and their interaction show a significant influence. The release rate of LMT was affected by humidity as well as type of excipients and their interactions.

Development and validation of ultraviolet spectrophotometric methods for lamivudine and zidovudine quantification in dissolution test

Context: In the development of a good analytical method, the selection of appropriate conditions for quantifying drugs is essential. The method validation should be determined before conducting the dissolution test. Aims: To develop and validate two analytical methods by UV spectrophotometry to quantify lamivudine and zidovudine in dissolution test. Methods: The dissolution conditions were 900 mL of dissolution medium (pH 1.2, pH 4.5, and pH 6.8), using paddles, at 75 rpm, and sampling time points of 5, 10, 15, 20, and 30 minutes. The analytical methods were developed by scanning analytical solutions in the UV region. The proposed methods were validated in accordance with the ICH guideline and the United States Pharmacopoeia. Results: Lamivudine showed wavelengths at 280 nm, 273 nm, and 270 nm in buffers at pH 1.2, pH 4.5, and pH 6.8, respectively; while zidovudine showed a wavelength at 266 nm in all three buffers. Regression analysis confirmed linearity (r2>0.998). Placebos and diluents showed no analytical interference. LOD and LOQ were lower than the linearity range. Recovery percentages were within 95% to 105%. RSD values were below 2% and 7% for repeatability and intermediate precision, respectively. No changes introduced modified the method response. The analytical solutions were stable until 24 hours. The results showed that Whatman No 41, No 42, and PVDF 0.45 µm filters can be used. Conclusions: The proposed analytical methods demonstrated linearity, specificity, accuracy, and precision. In addition, LOD and LOQ, robustness, stability of the analytical solution, and filter test showed satisfactory results.

Potential factors of Helicobacter pylori resistance to clarithromycin.

A comparative dissolution kinetics test (CDKT) and bioequivalence studies of generic proton pump inhibitors (PPIs) do not model pharmacological acid suppression (PAS) and pathological duodenogastric reflux (PDGR). This study aimed to model them in CDKT to assess drugs stability and potential pantoprazole-clarithromycin interactions. In CDKT, PDGR (dissolution medium pH 7.00±0.05, preexposure at pH 1.20±0.05) and PAS (pH 4.00±0.05) were modelled for original pantoprazole (OP) and its generics (GP1-4). In CDKT with high-performance liquid chromatography, dissolution gastric medium in adequate (pH 4.00±0.05) and inadequate (pH 1.20±0.05) PAS were modelled for original clarithromycin (OC) and its generics (GC1-4). After exposure in pH 7.00±0.05, pantoprazole was released from GP1 within 10min in the amount of 68.8%. In рН 4.00±0.05, 83.0% and 81.5% of pantoprazole were released from GP1 and GP4. When OP, GP2 and GP3 were placed in pH 7.00±0.05, pantoprazole was released in amount: 99.4%, 88.0% and 98.2%. Clarithromycin releasing from OC, GC1, GC2, GC3, GC4 in pH 4.00±0.05 was 93.5%, 91.6%, 92.9%, 79.4% and 83.0%. In pH 1.20±0.05: 9.7%, 6.7%, 8.5%, 33.3%, 28.8%. Destruction of enteric coats of some local pantoprazole generics in CDKT-models might be a potential factor for inadequate therapy.

Comments on “Solubility measurement and thermodynamic modeling of sertraline hydrochloride and clopidogrel bisulfate in deep eutectic solvent of choline chloride and malonic acid”

• Solubilization mechanism of a solute in salt form by a deep eutectic solvent was discussed. • Acidic component of studied DES can change pH of dissolution media. • The pH of final solution and precipitated form after equilibrium should be analyzed. The reported solubility study of sertraline hydrochloride and clopidogrel bisulfate in deep eutectic solvent (DES) has been analyzed from viewpoint of the solubility of a basic compound in salt form by a DES composed of malonic acid (an acidic hydrogen bond donor component) and choline chloride. Overall, evaluation of the solubilization mechanism of a DES composed of an acidic component on solubility of a solute in salt form could be found out by determining the pH of final solution and analyzing precipitate after equilibrium.

Comparative Dissolution Kinetics of Several Multisource Thioctic Acid Products

The relationship between dissolution and bioavailability is an example of the interdependency between the quality of a medicinal product and its safety and efficacy. The uniqueness of thioctic acid is that it can exist in an oxidised and a reduced form, showing lipophilic (lipoic acid) and hydrophilic (dihydrolipoic acid) properties. Bioavailability studies of thioctic acid are necessary to evaluate the expected therapeutic effect and mitigate side effects of the medicinal product.The aim of the study was to carry out equivalence dissolution testing to compare the release of thioctic acid from medicinal products produced by several manufacturers.Materials and methods: the study used a reference medicinal product and three multisource medicinal products by different manufacturers; more specifically, film-coated tablets containing 600 mg of thioctic acid. The experiment was carried out in dissolution media at pH of 6.8±0.05 and 1.2±0.05. Statistical analysis was performed by calculating the average amounts of the substance dissolved, the standard deviation (SD), and the relative standard deviation (RSD, %) using Microsoft Office Excel 2007.Results: The authors chose the testing conditions (dissolution media pH values of 6.8±0.05 and 1.2±0.05) taking into account the nature and characteristics of thioctic acid. The comparison of thioctic acid release profiles based on the calculation of the similarity factor (f2) showed that the dissolution profiles of multisource medicinal products 2 and 3 at pH 6.8 were equivalent to that of the reference medicinal product (more than 85% of the active pharmaceutical ingredient released within 15 minutes) and the dissolution profile of multisource medicinal product 1 was not equivalent to it (with f2 of 28).Conclusions: the established differences in the rate and degree of active ingredient release from the studied medicinal products may indicate possible differences in their pharmacological effectiveness in vivo.

Quality Control of Tramadol in Kisangani: Development, Validation, and Application of a UV-Vis Spectroscopic Method

Context: Substandard and falsified medicines are circulating in low-income countries mostly without any control. We availed a simple and not expensive UV-Vis spectroscopic method to evaluate the quality of tramadol in Kisangani before and during the Covid-19 period. Methods: For the analytical quantitative method, an experimental design was applied to set up the optimal levels of the selected factors, namely, pH of dissolution medium, type of cuvette, and wavelength. Taking into account the capsule pharmaceutical formulation within 80 - 120 μg&middotmL-1 concentration range, we analyzed 89 tramadol samples from pharmacies and hospitals of the six Kisangani municipalities. Results: pH showed a significant effect on absorbance, whereas quartz cuvette and wavelength did not. A typical 100 μg&middotmL-1 tramadol solution gave an absorbance of 0.64 at 272 nm. Validation highlighted a matrix effect observed with a 6% bias. A correction factor of 0.9372 allowed to improve the accuracy profile, which were then totally included within the 10% acceptance limits. Quality control revealed that 25 samples out of 89 were not compliant in terms of manufacturing license, registration status in DRC and content as well. Conclusion: This study showed that the strengthening of analytical strategy in Kisangani is a need.

Study on Dissolution Profile of Commercial Glyburide Tablets

The dissolution profile (DP) of a glyburide containing tablet - Daonil (supplied by Hoechst, Germany and used as the reference sample) was compared with those obtained from thirty-four commercial glyburide tablets in this study. Dissolution tests were performed by using a USP XXIII aparatus-II (paddle type) at 75 rpm, and three buffer solutions of pH 7.8, 6.8 and 5.8, respectively, were used as the media. Released percentages of the active ingredient were meassured at 15, 30, 45, 60, 90 and 120 minutes. SUPAC* f2 factor proposed by FDA was applied to verify the similarity between the DP of Daonil and that of each investigated samples. Results indicated that 10 out of 34 case samples (29.4%) were similar in DPs to Daonil 1 in all of three media. In the meantime, three samples (8.8%) gave similar profiles as the control in two media of pH 7.8 and pH 5.8. It was also found that thirteen tested samples (38.2%) were similar in DPs to Daonil in a buffer solution of pH 5.8, but different in both media of pH 6.8 and pH 7.8. Furthermore, only one case sample gaved a completely different profile compared with that of Daonil no matter what pH of dissolution media was. Finally, statistics on the number of tested samples having similar DPs as Daonil in individual media are as follows: 13 in pH 7.8 (38.2%); 17 in pH 6.8 (50%); and 33 in pH 5.8 (97.1%).

Sustained-release Theophylline Matrix Tablet Using Hydrophilic Polymers: Effects of Agitation Rates and pH on Release Kinetics

Background and Objective: Modified-release tablet of theophylline that can increase its usefulness despite narrow therapeutic index and short half-life, is being formulated. However, the rate and extent of release of a sustained-release delivery system can be affected by some factors. This work is aimed at investigating the effect of agitation rates and pH of dissolution medium on release kinetics of sustained-release theophylline tablet formulated using hydrophilic polymers.
 Materials and Methods: Theophylline granules was formulated using 3 polymers (HPMC, SCMC and Sodium alginate) to form 3 batches of granule by wet granulation method, using 95% ethanol. The granules compacted to batches of sustained-release matrix tablets. The tablet batches were characterized for tablet properties, and dissolution studies carried out using simulated gastric and intestinal fluid separately at different agitation rates. The data from dissolution studies were subsequently fitted into 4 drug release kinetics models.
 Results: The swelling of the 3 polymers over time was noteworthy, although there was no significant difference between them. The release kinetic followed the Higuchi model and zero-order releasing more than 90% over 8 hours period, with t10 and t90 released at 14 minutes and 6.8 hours respectively. The mechanical properties of the tablets were within the acceptable limit.
 Conclusion: The agitation rate and pH of the medium had no significant effect on the release of the theophylline from the batches of matrix tablets except in the case of F1 which showed a marginally significant effect.

Utilization of Diluted Compendial Media as Dissolution Test Solutions with Low Buffer Capacity for the Investigation of Dissolution Rate of Highly Soluble Immediate Release Drug Products.

Research from the past decade has shown that the buffer capacities of intestinal fluids are much lower than those in the media used for dissolution test of many solid formulations. The purpose of this study was to elucidate the effect of buffer capacity on the dissolution profiles of highly soluble drug products, using metoclopramide (a biopharmaceutics classification system [BCS] class III drug) tablets as a model. The dissolution profiles of three metoclopramide products were obtained in Japanese pharmacopeia dissolution medium (pH 1.2 and 6.8), diluted medium with low buffer capacity comparable to that of gastrointestinal fluid, and other biorelevant media. One product showed slower dissolution in the medium with lower buffer capacity (bio-relevant, diluted compendial solution), but substantially similar dissolution in the compendial test solutions. Disintegration difference was implied to be involved in the different dissolution profiles depending on the medium buffer capacity. This study indicated the importance of media buffer capacity as a factor inducing different dissolution between products of highly soluble active pharmaceutical ingredients. The diluted compendial media would be a useful alternative to biorelevant media for the detection of the different formulation performances depending on the buffer capacities.

In-Vitro and In-Vivo Evaluation of Velpatasvir- Loaded Mesoporous Silica Scaffolds. A Prospective Carrier for Drug Bioavailability Enhancement.

The limited aqueous solubility of many active pharmaceutical ingredients (APIs) is responsible for their poor performance and low drug levels in blood and at target sites. Various approaches have been adopted to tackle this issue. Most recently, mesoporous silica nanoparticles (MSN) have gained attention of pharmaceutical scientists for bio-imaging, bio-sensing, gene delivery, drug solubility enhancement, and controlled and targeted drug release. Here, we have successfully incorporated the poorly water soluble antiviral drug velpatasvir (VLP) in MSN. These spherical particles were 186 nm in diameter with polydispersity index of 0.244. Blank MSN have specific surface area and pore diameter of 602.5 ± 0.7 m2/g and 5.9 nm, respectively, which reduced after successful incorporation of drug. Drug was in amorphous form in synthesized VLP-loaded silica particles (VLP-MSN) with no significant interaction with carrier. Pure VLP showed poor dissolution with progressive increment in pH of dissolution media which could limit its availability in systemic circulation after oral administration. After VLP loading in silica carriers, drug released rapidly over a wide range of pH values, i.e., 1.2 to 6.8, thus indicating an improvement in the solubility profile of VLP. These particles were biocompatible, with an LD50 of 448 µg/mL, and in-vivo pharmacokinetic results demonstrated that VLP-MSN significantly enhanced the bioavailability as compared to pure drug. The above results clearly demonstrate satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement with VLP-MSN.

Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers.

The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel® 60 HG) on the dissolution behavior of two cocrystals derived from nitazoxanide (NTZ), viz., nitazoxanide-glutaric acid (NTZ-GLU, 1:1) and nitazoxanide-succinic acid (NTZ-SUC, 2:1), was explored. Powder dissolution experiments under non-sink conditions showed similar dissolution profiles for the cocrystals and pure NTZ. However, pre-dissolved cellulosic polymer in the phosphate dissolution medium (pH 7.5) modified the dissolution profile of NTZ when starting from the cocrystals, achieving transient drug supersaturation. Subsequent dissolution studies under sink conditions of polymer-based pharmaceutical powder formulations with NTZ-SUC cocrystals gave a significant improvement of the apparent solubility of NTZ when compared with analogous formulations of pure NTZ and the physical mixture of NTZ and SUC. Scanning electron microscopy and powder X-ray diffraction analysis of samples recovered after the powder dissolution studies showed that the cocrystals undergo fast dissolution, drug supersaturation and precipitation both in the absence and presence of polymer, suggesting that the solubilization enhancement is due to polymer-induced delay of nucleation and crystal growth of the less soluble NTZ form. The study demonstrates that the incorporation of an appropriate excipient in adequate concentration can be a key factor for inducing and maintaining the solubilization of poorly soluble drugs starting from co-crystallized solid forms. In such a way, cocrystals can be suitable for the development of solid dosage forms with improved bioavailability and efficacy in the treatment of important parasitic and viral diseases, among others.

Application of statistical design on the early development of sustained-release tablet containing ivy leaf extract

The aim of this study was to develop a sustained-release (SR) tablet of ivy leaf extract (ILE) that exhibits robust dissolution profiles unaffected by pH and mechanical stress in the gastrointestinal (GI) tract using statistical design. The response surface design was used to study the effect of type and amount of sustaining polymer on the drug release over time. The type and amount of sustaining polymers were set as factors. The percentages of dissolved hederacoside C, as an indicator substance of ILE, at 6, 12, and 24 h were set as the responses. The highest desirability value was obtained when 26.09% of HPMC K15 M (hydroxypropyl methylcellulose, 15,000 mPa s) was used among the various polymers tested. The granules and tablets prepared with this composition showed acceptable physical properties (bulk density, tapped density, angle of repose, thickness, hardness, and friability). The drug release profiles of the SR tablet exhibited non-Fickian mechanism close to zero-order release based on the Korsmeyer-Peppas model regardless of the pH of dissolution media and the paddle speed of the dissolution tester. Overall, the present study suggested a new statistical approach to the development of SR tablets containing herbal medicine and successfully developed the tablets.

Design of Experiments Approach to Discriminatory Dissolution Method Development of Poorly Soluble Drug in Immediate Release Dosage Form

Abstract: Aim: The study involved design of experiment guided discriminatory dissolution method development for poorly soluble, ezetimibe tablets. Objective: In the current scope of study, ezetimibe tablets are selected as a suitable drug product candidate to evaluate the application of design of experiments in discriminatory dissolution method development for poorly soluble drug. Ezetimibe is practically insoluble in all the aqueous buffers. Methodology: 2-Level factorial design is selected as suitable model to build the experimental setup. Different factors like pH of dissolution media, sodium lauryl sulphate concentration, dissolution media volume and agitation speed (RPM) are selected for the study and dissolution % release at 5, 10, 15, 20, 45 min and % RSD of dissolution values at 20 min were selected as responses based on prior experience. The responses are evaluated for statistical significance and for adequacy of the built design with the help of different tools like ANOVA and diagnostic graphs. Results: It is observed that pH of dissolution media, surfactant concentration are having minimal positive effect on all of the responses. Whereas agitation speed and dissolution media volume were having significant positive effect on all responses, except for % RSD at 20 min and is inversely proportional to agitation speed. Conclusion: With the current scope of study design of experiments as an effective tool for discriminatory dissolution method development is employed to prove adequacy. Selected solutions from predictions were executed for experimental results and were compared against predictions to validate model. Key words: DoE, Discriminatory dissolution method, Ezetimibe tablets, DoE aided dissolution method development.

Formulation and evaluation of polymeric nanoparticles of an antihypetensive drug labetalol

Labetalol is an adrenergic receptor blocking agent used in the treatment of hypertension and characterized by high solubility and high permeability which corresponds to BCS class I drug. Plasma half life ranges from 6 & bioavailability is 25%. Ethyl cellulose was used as a rate controlling polymer. Effects of addition of ethyl cellulose on in vitro dissolution were studied. Nanoparticles were formulated using different polymer ratios. In vitro drug release was carried out by using USP Type II at 50 rpm in 900 ml of acidic dissolution medium (pH 1.2) for 2 hours, followed by 900 ml alkaline dissolution medium (pH7.4) for 12 hours. Mean dissolution time is used to characterize drug release rate from a dosage form. Several kinetic models were applied to the dissolution profiles to determine the drug release kinetics. Excipients are selected by FTIR studies. Finally the nanoparticles were evaluated for various characteristics like encapsulation efficiency, percentage yield, partial size and the In vitro release for 12 hrs. The nanoparticles were found to be discrete, spherical, and free-flowing. The nanoparticles were uniform in size, and the microencapsulation efficiency was in the range of 52.5-81.7%. The surface morphology of prepared Labetalol nanoparticles was observed under scanning electron Microscopy. Nanoparticles had good spherical geometry. The stability study was performed at 40ºC ± 2ºC and 75 ± 5% RH for 6 months.
 Keywords: Nanoparticles; Labetalol, Hypertension, Ethyl Cellulose, Dissolution, entrapment efficiency.

Effects of Dissolution Medium pH and Simulated Gastrointestinal Contraction on Drug Release From Nifedipine Extended-Release Tablets*

In contrast to nifedipine matrix-based extended-release dosage forms, the osmotic pump drug delivery systems have a zero-order drug release independent of external variables such as pH, agitation rate, and dissolution media. The objective of this study focuses on the in vitro evaluation of the mechanical properties of osmotic pump and polymer matrix-based formulations in dissolution media, and the potential impacts that media pH and simulated gastrointestinal contraction have on drug release. Two strengths of osmotic pump product A and polymer matrix-based product B were used in this study. An in-house system was developed with the capability of applying mechanical compression and monitoring mechanical properties of sample during dissolution testing. A United States Pharmacopeia or an in-house apparatus was used for dissolution testing under various conditions. Compared to the product A, the mechanical properties of the product B change significantly at various pHs and mechanical compressions. The results suggest that polymer matrix-based products bear a risk of formulation-related interactions with the gastrointestinal tract during in vivo drug dissolution, especially in the case of concomitant pH and gastric contractile changes. Modified dissolution testing devices may help formulation scientists in product development and provide regulatory agencies with an additional metric for quality assurance of drug products.

Development of pH Independent Drug Release System for Dipyridamole

Abstract: Introduction: Dipyridamole is an Anti-platelet agent exhibits release problems at higher pH of small intestine due to its pH dependent solubility and precipitation followed by interruption of drug release from dosage form. To overcome this extended release formulation was developed by using pH modulating agent (tartaric acid). Objective: Present study was undertaken with a view of the formulations evaluated by performing dissolution testing on developed extended released tablets. Method: development of dissolution method at different time points and USP Apparatus 1 (basket) and 2 (paddle) at rotating speeds of 50 or 100 rpm used to evaluate the release characteristics of the formulations. Furthermore, solubility and in vitro dissolution studies of formulated tablets were performed at pH values of 1.2 and 5.5. Results: In this study we found increasing volume of dissolution medium pH 5.5 phosphate buffers drug precipitation is increased. The developed dissolution method was validated according to ICH guidelines for various parameters such as specificity, accuracy, precision, and stability. The dissolution method was confirmed by determining the dissolution rate of extended released Dipyridamole tablets containing pH modulating agent. The best in vitro dissolution profile was obtained using pH 5.5 phosphate buffer as the dissolution medium (500 ml) stirred at 100 rpm. A comparison of the dissolution profiles in official and developed media showed significant differences based on f1 and f2 values. Conclusoni: The developed dissolution test exhibited a higher capacity than the compendia methods in differentiating the release profiles of pH independent extended release tablets. It can be applied during formulation development and quality control analysis of pH independent extended release tablets for evaluation of the effects of pH modifier in dissolution medium and processing parameters. Key words: Tartaric acid, Dissolution media, Extended release Dipyridamole Tablets.

Effect of lipid and cellulose based matrix former on the release of highly soluble drug from extruded/spheronized, sintered and compacted pellets

BackgroundThe study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol using hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control the release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular diseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl monostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were used in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control the burst release of Atenolol.MethodFor this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology (RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes (GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were performed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order, first order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of DDsolver, an excel based add-in program.ResultsThe formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model (R2 = 0.975–0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy showed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The cross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that the optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug release for 12 h.ConclusionExtended-release encapsulated, and compacted pellets were successfully prepared after the combination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in addition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is an effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.