Hydroxypropyl Methylcellulose E5 Research Articles

Pioglitazone-loaded three-dimensional composite polymeric scaffolds: A proof of concept study in wounded diabetic rats.

Diabetic patients suffer from impaired wound healing. In this study, the anti-diabetic drug, Pioglitazone hydrochloride (PG), was loaded in three-dimensional (3D) composite scaffolds (SC) designed to be applied topically for the management of diabetic wounds. Hydroxypropyl methyl cellulose (HPMC) of different molecular weight (E5, K4M or K15M) were used, in different ratios, with chitosan (CS) for the preparation of the 3D-SC. Investigations to examine the prepared SCs revealed that SC-F3 composed of CS /HPMC E5 (2:1) attained the highest porosity (99.12 ± 5.01), highest water absorption capacity % (300.09 ± 20.20), and attained the fastest drug release profile (p < 0.05), with release kinetics following the diffusion model. SEM microphotographs showed the highly porous structure of SC-F3. According to the modified Draize test, the selected 3D-SC (the medicated as well as the unmedicated) showed to be safe for skin application (PII = 0). During the in-vivo studies, both the selected PG-loaded SC and the unmedicated SC showed a significant improvement in the healing process compared to the untreated group, this was evidenced by the measurement of wound contraction % [627% and 467%, respectively, p < 0.05], as well as the level of some biomarkers (TNF-α, VEGF and MMP-9). PG-loaded SC had a significantly better effect than the unmedicated SC (p < 0.05). Histopathological studies confirmed the complete tissue regeneration and healing process after the use of the selected PG-loaded scaffolds. The current study presents a feasible approach to support diabetic wound healing using a simple and safe formulation.

Development and evaluation of rapidly dissolving buccal films of naftopidil: in vitro and in vivo evaluation

Objectives: Development and evaluation of rapidly dissolving film for intra-oral administration of naftopidil.Significance: Formulation of naftopidil in the form of rapidly dissolving buccal film can eliminate the dissolution problem of naftopidil and provide a greater chance for direct absorption into the systemic circulation bypassing the presystemic metabolism. This can improve the oral bioavailability. In addition, this film guarantees patient compliance and is suitable for geriatric patients.Methods: Rapidly dissolving film utilized hydroxypropyl methylcellulose E5 and polyvinylpyrrolidone K30 as the main components. The drug was loaded in pure form or after co-grinding with citric and/or tartaric acid. A solution of naftopidil in plurol oleique, labrasol, and tween 80 self-microemulsifying drug delivery systems (SMEDDS) was also loaded. The interactions of the drug with the excipients were monitored using thermal analysis, Fourier transform infrared spectroscopy, and X-ray diffraction. Naftopidil dissolution was monitored and selected films were used to assess the bioavailability after buccal administration to rabbit. Unprocessed drug suspension was administered orally and used as a reference.Results: Incorporation of naftopidil in the film developed a new crystalline structure. The crystallinity of drug was abolished in the presence of organic acids or SMEDDS. The rapidly dissolving films showed fast liberation of the drug irrespective to the composition. Those films enhanced the bioavailability of naftopidil compared to orally administered suspension with SMEDDS containing film being superior.Conclusion: The study introduced rapidly dissolving buccal film for enhanced dissolution and bioavailability of naftopidil.

FORMULATION AND EVALUATION OF ANTIPARKINSON’S DRUG INCORPORATED TRANSDERMAL FILMS

Objective: Ropinirole suitable for transdermal delivery due to its small molecular size (260.37 g/mol), optimum log p (2.3), and low oral bioavailability (50%) due to first-pass metabolism, the short elimination half-life of 4–6 h. Dose of drug is 6 mg/day. Hence, in the present study, an attempt was made to deliver antiparkinson’s drug through transdermal route in the form of transdermal film to attain sustained release using different concentration of drug, polymers stabilizers.&#x0D; Methods: Among the different formulations of matrix type (F1 to F5), F2 and F4 formulations were optimized based on crystallinity. These formulations were carried out for in vitro permeation studies. Out of these two formulations, F4 formulation showed target drug release.&#x0D; Results and Discussion: The formulation F4 containing 2 mg drug, 600 mg hydroxypropyl methylcellulose E15 and 50 mg of Eudragit RS 100 was selected as optimized formulation, after considering its microscopic examination throughout stability, % drug content (98.4%), drug permeated through the cellophane membrane at the end of 72 h, and evaluation of physicochemical characterization parameters such as thickness, weight variation, flatness, folding endurance, moisture content, and tensile strength.&#x0D; Conclusion: The results of physicochemical characterization were ensured the stability of the films. The drug permeation profile was also found to follow Higuchi kinetic model.

Nanocrystal Formulation Improves Vaginal Delivery of CSIC for HIV Prevention.

5-Chloro-3-phenylsulfonylindole-2-carboxamide (CSIC) is a highly potent non-nucleoside reverse transcriptase inhibitor (NNRTI) with potential for use in topical prophylaxis against HIV transmission. However, the hydrophobic nature of CSIC limits its administration through vaginal route. In this study, we developed nanocrystals of CSIC to potentially improve the aqueous solubility and intracellular uptake of CSIC in vitro and in vivo. CSIC nanocrystals were manufactured and stabilized with Pluronic F98 and hydroxypropyl methylcellulose E5. Transmission electron microscopy showed CSIC nanocrystals to be needle-like. Dynamic light scattering measurements showed a hydrodynamic size of 243nm (polydispersity index < 0.3) and near neutral surface charge (- 7.8mV). Particle size was maintained for at least 7days in the liquid state and for at least 5months after lyophilization. Drug content in the CSIC nanocrystal formulation (nanosuspension) was 0.8mg/mL, which is 1000 times higher than the aqueous solubility of CSIC. In vitro release study showed that over 90% of CSIC was released from the nanocrystal formulation in a linear fashion over a period of 4days. Importantly, CSIC nanocrystals showed equivalent cell-based anti-HIV activity (EC50 ~ 1nM) as that of non-formulated drug. In vitro studies demonstrated rapid macrophage uptake of CSIC nanocrystals via both energy-dependent (endocytosis) and independent processes. In vivo studies in Swiss Webster female mice showed that the nanocrystal formulation significantly improved CSIC delivery to mouse cervicovaginal tissues following intravaginal instillation. In summary, nanocrystals are a promising formulation approach for topical delivery of CSIC for protection against HIV sexual transmission.

Modified-release oral pellets for duodenum delivery of doxycycline hyclate.

To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY-containing modified-release oral pellets (DMOP) coated with hydroxypropyl methylcellulose phthalate HP-55 (HPMCP HP-55) and hydroxypropyl methylcellulose E15 (HPMC E15) appear to be a reasonable choice. This coating layer dissolves at pH 5.5, which is the pH of the duodenum, but not at a gastric pH (1.2). The formulation and preparation of DMOP were optimized, and a scale-up test was performed. The results showed that the production reproducibility was acceptable, and the quality of DMOP well met the standards of Chinese Pharmacopeia (Ch.P, 2015 edition). Notably, the accumulated DOXY release was lower than 50% at pH 1.2 (20 min) and higher than 85% at pH 5.5, which met the USP40-NF35 standard for DOXY modified-release formulations. Moreover, the storage stability of DMOP with different packages was investigated by stress testing, accelerated and long-term testings. The stability of DMOP was maintained up to 12 months, in terms of DOXY content and in vitro release behavior. The results seem to suggest that DMOP could be a promising duodenum delivery system.

Design, Development and Characterization of Nifedipine Microspheres

Back ground: Nifedipine is a calcium channel blocker and is used in treatment of angina of angina pectoris and hypertension. Nifedipine readily and almost completely absorbed from GIT, but undergoes first pass metabolism, resulting in low oral bioavailability is about 50%.&#x0D; Aim: The aim of the present study was to prepare and evaluate the microspheres of nifedipine with a goal of improving the bioavailability and giving a prolonged release of drug.&#x0D; Method: Emulsification (o/w) solvent evaporation method was employed in the preparation of nifedipine microparticles using ethyl cellulose and combination of ethyl cellulose and hydroxypropyl methylcellulose as the polymers.&#x0D; Results: FT-IR spectra of physical mixture showed no significant shifting of the peaks therefore it reveals that the drug is compatible with the polymer used. The percentage yield obtained in all the formulations was good and in the range of 59.25-94.44%. Among all the formulations, formulation with combination of ethyl cellulose and hydroxypropyl methylcellulose polymers M9 showed high amount of drug release i.e. (91.23%) in 12hrs. Drug release from microspheres with small mean particle size was faster than those with large mesh particle size and followed Higuchi model of kinetics.&#x0D; Conclusion: The obtained results could be used as essence to develop microspheres, which bypasses first-pass metabolism and results in the improvement of bioavailability. Hence, the present study has been a satisfactory attempt to formulate microspheres of nifedipine, with a view of improving its oral bioavailability and giving a prolonged release of drug.&#x0D; Keywords: Microspheres, nifedipine, hydroxypropyl methylcellulose E5, ethyl cellulose.

FORMULATION AND EVALUATION OF RAMIPRIL MOUTH DISSOLVING FILMS

Objective: The present investigation was aimed at preparation and evaluation of mouth dissolving films (MDFs) of Ramipril to enhance patient convenience, compliance and to improve bioavailability.&#x0D; Methods: MDFs with 0.5% w/w Ramipril were prepared by a solvent casting method using a wet film applicator. The effects of film formers, wetting/solubilizing, saliva stimulating agents and film modifiers on the physicomechanical and in vitro Ramipril release from MDFs were evaluated.&#x0D; Results: The MDFs prepared were transparent, smooth and showed no re-crystallization upon storage. MDFs casted with hydroxypropyl methylcellulose (HPMC) E3 as film former and polyethylene glycol (PEG-400) as plasticizer showed superior Ramipril release rates and good physicomechanical properties when compared to MDFs with E5 and E15 as film formers. HPMC E3 MDFs with polyvinyl pyrrolidone K30 (PVP K30) and sodium lauryl sulphate (SLS) gave superior drug release properties than MDFs without PVP K30 and SLS. The HPMC E3 MDFs with citric acid (CA) as saliva stimulating and xylitol as soothing agent gave significantly superior in vitro drug release than the MDFs without CA and xylitol. Release kinetics data reveals diffusion as a drug release mechanism.&#x0D; Conclusion: From the obtained results, it can be concluded that the administration of Ramipril as MDF may provide a quick onset of action with enhanced oral bioavailability and therapeutic efficacy.

Fabrication and evaluation of dental fillers using customized molds via 3D printing technology

In view of the high incidence and long-term treatment of dental caries, personalized dental fillers with long therapeutic action have broad application prospects in the dental clinic. The objective of this study was to fabricate and evaluate novel dental fillers using state-of-the-art 3D printing technology. Tinidazole (TNZ), a commonly used antibacterial drug in the dental clinic, was chosen as the model compound. Models of molars with carious cavities were obtained via 3D scanning. TNZ dental fillers were indirectly produced by thermal pressing using customized 3D printed molds. In addition, bio-relevant in vitro dissolution and mechanical testing methods were developed using customized 3D printed release and compression molds, respectively. It was observed that the formability, mechanical properties, and release behavior of the TNZ dental fillers were affected by mold materials, plasticizers, and release modifiers. The developed dental fillers were capable of sustained releasing TNZ over one week. The TNZ release characteristics can be tailored based on clinical requirements by varying hydroxypropyl methylcellulose E5 (HPMC-E5) concentrations and filler dimensions. Moreover, computational simulation based on the finite element method showed that the biomechanical behavior of the TNZ dental fillers met the daily use requirement. The present study demonstrated that the state-of-the-art 3D printing technology can be used to design and fabricate personalized dental fillers with high mechanical strength and “on-demand” drug release characteristics.

Overcoming Poor Tabletability of Bulky Absorption Enhancers by Spray Drying Technology

Absorption enhancers are often a major component of solid oral peptide formulations as compared to the active pharmaceutical ingredient and excipients. This commonly results in poor tabletability that is hard to mitigate in direct compaction by addition of small amounts of excipients. To improve the tabletability of bulky absorption enhancers, the model absorption enhancers, sodium cholate and deoxycholic acid, were co–spray-dried with hydroxypropyl methylcellulose E5, where the percentage of absorption enhancers was not lower than 90% (w/w). The physicochemical properties of the resulting powders were assessed by laser diffraction, scanning electron microscopy, X-ray powder diffraction, thermogravimetric analysis, and differential scanning calorimetry. The powders were compressed into tablets, and the tabletability was evaluated. Co–spray drying with 10% of hydroxypropyl methylcellulose significantly improved the tabletability of the both absorption enhancers. Moreover, it was demonstrated that small particle size and amorphous state rather than high moisture content contributed to the improved tabletability of the spray-dried powders. The study suggests that spray drying technology can be promising to overcome the poor tabletability of oral peptide formulation consisting of large amounts of absorption enhancers.

Development of Rizatriptan Mouth Dissolving Films: A Fast Absorbing Drug Delivery System for Effective Treatment of Migraine

The aim of this investigation was to develop Rizatriptan (RIZ) mouth dissolving films (MDFs)and evaluate the effect of formulation variables like film thickness, plasticizers, film formers and solubilizing agents on physicomechanical, chemical and drug release properties of MDFs. MDFs were prepared (using wet film applicator, a commercially scalable technique) using Hydroxy propyl methyl cellulose (HPMC) of different viscosity grades (E3, E5 and E15) as film former, PEG 400 and glycerol as plasticizers. FTIR studies showed no RIZ-excipient interactions in the MDF formulations. Photomicrographs together with DSC and X-RD studies confirmed the absence of RIZ recrystallization within the MDFs. MDFs of higher film thickness were brittle with low tensile strength values indicating an inverse relationship between film thickness and tensile strength. Whereas, increase in polymer viscosity increased the tensile strength of MDFs and about a 2.6fold increase in tensile strength was obtained with HPMC E15 MDFs compared to E3. In vitro drug release studies revealed that higher film thickness and polymer viscosities delayed the RIZ release from MDFs and the release was in the order of E3>E5>E15. Addition of solubilizing agents (PVP K30 and SLS) to the E3 formulations resulted in 2 and 1.43 fold faster RIZ release compared to formulations without them. Overall, F11 formulation (1% w/w RIZ+7.5% w/w HPMC E3+0.04% w/w PVP K30+0.5% w/w PEG 400) showed faster disintegration (within 8sec) and RIZ release rates (complete release was obtained in 60sec) compared to other formulations. The MDFs showed 98102% RIZ content even after 6months time period indicating that the RIZ was stable in MDF formulations.

Overcoming Poor Solubility of Dimenhydrinate: Development, Optimization and Evaluation of Fast Dissolving Oral Film.

Purpose: To develop fast dissolving oral film to address vomiting and nausea in pediatric population.Methods: Oral films of Dimenhydrinate were prepared by solvent casting method by using hydroxypropylmethyl cellulose E5 (HPMC E5), polyethylene glycol 400 (PEG 400) and croscarmellose sodium. Solubility of dimenhydrinate was enhanced by ethanol as a co-solvent. To make dimenhydrinate palatable sodium saccharin and peppermint oil were used. All films were evaluated for mechanical parameters, surface pH, morphology, disintegration time and percent dissolution.Results: Films were smooth, acceptable and white in colour. For optimized batch, drug content (99.106%), disintegration time (25 sec), dissolution (99.10% in 210 sec), surface pH (6.81) were acceptable.Conclusion: Optimized batch, due to its potential to deliver through fast dissolving film, can be developed for clinical use.

FORMULATION AND EVALUATION OF FAST DISSOLVING FILM OF LORNOXICAM

Objective: The aim of the present work was to formulate and evaluate fast dissolving film containing lornoxicam.Materials and Methods: To prepare the film, hydroxypropyl methylcellulose E5 and polyvinyl alcohol (PVA) were used as film-forming polymers by solvent casting method. Glycerine was used as plasticizer, aspartame, and mannitol as sweetener. All prepared films were evaluated for its weight variation, disintegration time, thickness, drug content, pH, dissolution study, and folding endurance. The drug-excipients compatibility study was done using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR).Results: Satisfactory results obtained when PVA was used as film-forming polymer, and the drug was dispersed in the polymer solution using poloxamer 407 as a solubilizing agent. Formulation F2 is considered as the optimized formulation as it showed good folding endurance (&gt;300), faster disintegration rate (30 s), and maximum in vitro drug release (87%) within 5 min. DSC and FTIR studies showed no interaction between drug and the polymers.Conclusion: It can be concluded from the study that the fast dissolving film can be prepared for poorly water-soluble drug lornoxicam using PVA as a suitable film-forming polymer.

Storage stability and solubilization ability of HPMC in curcumin amorphous solid dispersions formulated by Eudragit E100

The present study elucidated the advantages of using hydroxypropyl methylcellulose E5 (HPMC) as auxiliary excipient in maintaining storage stability and solubilization ability for curcumin amorphous solid dispersion (Cur ASDs) formulated by Eudragit E100 (E100). Polarized light microscopy and in vitro dissolution experiment was applied for confirming the ability of HPMC on inhibiting crystallization thereby maintaining storage stability in Cur ASDs. Meanwhile, as a non-ionic surfactant, HPMC can form micelles in pH 1.0 hydrochloric acid and played a role in solubilization ability on Cur. Critical micelle concentration (CMC), molar solubilization ratio (MSR) and micelle-water partition coefficient Kmc of surfactants (HPMC, E100/HPMC 1:1 and E100/HPMC 6:1) in pH 1.0 hydrochloric acid were calculated to determine the solubilization ability of surfactants. The results showed that the solubilization ability of E100/HPMC 6:1 was the best and the solubilization mechanism of E100/HPMC 6:1 was also different from HPMC and E100/HPMC 1:1.

FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILM OF ANTI-ALLERGIC DRUG

The aim of present work was the development of fast dissolving oral film of Loratadine to overcome the limitations of current routes of administration, to provide immediate action and increase the patient compliance. To improve the bioavailability of the drug, fast dissolving oral film were formulated using different grades of Hydroxy Propyl Methyl Cellulose(HPMC) and various plasticizers like Polyethylene Glycol(PEG) 400, glycerol, Propylene glycol(PG) by solvent casting method. The formulated films were evaluated for film thickness, surface pH, folding endurance, weight variation, % moisture loss, exvivo permeation study, tensile strength, % elongation, drug content uniformity, in vitro dissolution studies,in vitro disintegration test and in vivo study. The optimized formulation (F9) containing HPMC E5 and glycerol showed minimum disintegration time (10.5 s), highest in vitrodissolution (92.5%) and satisfactory stability. Ex vivo permeation study of optimized formulation showed a drug release of 80.6% within 10 min. The milk induced leucocytosis inrat proved that fast dissolving oral films of Loratadine produced a faster onset of action compared to the conventional tablets. These findings suggest that fast dissolving oral film of Loratadine could be potentially useful for treatment of allergy where quick onset of action is required.

Frovatriptan loaded hydroxy propyl methyl cellulose/treated chitosan based composite fast dissolving sublingual films for management of migraine

We aimed to prepare frovatriptan succinate monohydrate (FSM) loaded sublingual films to provide direct entry of FSM into systemic circulation by escaping first-pass effect and thus providing quick onset of action. Solvent casting method was used to prepare FSM films employing hydroxypropyl methyl cellulose E15 (HPMC E15) as film forming agent, mannitol as release modifier, glycerine as plasticizer and chitosan or carboxymethyl cellulose sodium (CMCNa) as mucoadhesive polymer at low concentration. Placebo films were made using HPMC E15, glycerine and mannitol to get optimized ratio of these excipients giving acceptable films with desired physicochemical properties of films i.e. folding endurance (>300) and disintegration time (<2 min). Furthermore, the drug was loaded in the optimized ratio of excipients along with 1–2% w/w of mucoadhesive polymers i.e. chitosan or CMCNa to provide more intimate contact of drug to sublingual mucosa. Finally optimized film was selected based on acceptable physicochemical properties like disintegration time (<2 min), high dissolution (89.9% in 5 min) and maximum permeability. The pharmacodynamics models further confirmed the antimigraine ability of the developed optimized sublingual film. This research shows the aptness of FSM containing sublingual films as an alternative approach to control the migraine.

PREPARATION AND EVALUATION OF RAPIDLY DISSOLVING ‎TABLET OF TELMISARTAN

Objective: The aim of this work was to enhance the dissolution rate of telmisartan with the goal of developing fast disintegrating tablets (FDTs) with subsequent rapid dissolution for sublingual administration. Methods: Binary solid dispersion systems (SDS) were prepared by solvent evaporation technique for the drug with Gelucire 44/14 (formula A), polyethylene glycol 4000 (PEG4000) (formula B), Pluronic F68 (formula C), hydroxypropyl methylcellulose E5 (HPMC E5) (formula D), and finally by using sodium bicarbonate with the drug in (0.5: 1) ratio (formula E), and (1:1) ratio (formula F). These systems were evaluated for drug dissolution in addition to the physicochemical changes of the drug utilizing FTIR spectroscopy, thermal analysis, and X-ray diffraction. Results: The prepared formulations using sodium bicarbonate significantly enhanced the dissolution rate of the drug compared with those prepared using different types of polymers. The order of enhanced dissolution of the drug in the first 5 min Q5 (%) was: formula E > F > D5, where the % drug dissolved was 88.94 ± 1.31, 84.77 ± 1.1 and72.6 ± 0.81 (mean + SD) for each formula, respectively. Formula E was selected for the formulation of the rapidly dissolving tablet of telmisartan since it showed enhanced dissolution of the drug, more palatable taste in the buccal cavity, relatively inexpensive material and ease of processing compared with a solid dispersion prepared using polymer. Conclusion: Sodium bicarbonate can be utilized in the preparation of telmisartan FDT with fast dissolution rate. Conclusion: sodium bicarbonate can be utilized in the preparation of telmisartan FDT ‎with fast dissolution rate.‎

Formulation and Characterization of Fast-Dissolving Sublingual Film of Iloperidone Using Box-Behnken Design for Enhancement of Oral Bioavailability.

Iloperidone is a second-generation antipsychotic drug which is used for the treatment of schizophrenia and has very low aqueous solubility and bioavailability. This drug also undergoes first-pass metabolism. The aim of this work is to formulate fast-dissolving sublingual films of iloperidone to improve its bioavailability. Sublingual films were prepared by solvent casting method. Hydroxypropyl methyl cellulose E5, propylene glycol 400, and transcutol HP were optimized using Box-Behnken three-level statistical design on the basis of disintegration time and folding endurance of films. Iloperidone:hydroxypropyl-β-cyclodextrin kneaded complex was used in films instead of plain drug due to its low solubility. Optimized film was further evaluated for drug content, pH, dissolution studies, ex vivo permeation studies, and pharmacokinetic studies in rats. The optimized film disintegrated within 30s. The in vitro dissolution of the film showed 80.3 ± 3.4% drug dissolved within first 5min. In ex vivo permeation studies using sublingual tissue, flux achieved within first 15min by film was around 117.1 ± 0.35 (mcg/cm2/h) which was ten times more than that of plain drug. This formulation showed excellent uniformity. AUC and Cmax of film were significantly higher (p < 0.001) as compared to plain drug and relative bioavailability of the films was 148% when compared to the plain drug. Thus, this study showed optimized fast-dissolving sublingual film to improve permeation and bioavailability of iloperidone. Fast-dissolving films will be customer-friendly approach for geadiatric schizophrenic patients.

Impact of HPMC on inhibiting crystallization and improving permeability of curcumin amorphous solid dispersions

The purpose of this paper was to elucidate the impacts of hydroxypropylmethyl cellulose E5 as assistant excipient on inhibiting crystallization and improving membrane permeability in curcumin amorphous solid dispersions that formulated by Eudragit E100. Intermolecular interactions formed between curcumin and polymers were probed using in situ Raman imaging and infrared spectroscopy. The abilities of hydroxypropylmethyl cellulose E5 in inhibiting crystallization and improving membrane permeability were confirmed by fluorescence spectroscopy, dynamic light scattering analysis and in vitro permeability experiment. The results demonstrated hydroxypropylmethyl cellulose E5 was significant in maintaining the amorphous drug concentration owing to the hydrogen bond interactions formed with curcumin, rending its ability to inhibit crystallization by reducing drug droplet size. Furthermore, the addition of hydroxypropylmethyl cellulose E5 in curcumin amorphous solid dispersions promoted drug membrane permeability through lowering the order level of phospholipid bilayer layer.

Polymorphic transformation as a result of atovaquone incompatibility with selected excipients

Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy, and hot-stage microscopy were employed to evaluate the drug–excipient compatibility of atovaquone with commonly used tablet excipients. The DSC curves of pure drug and excipients were compared with their physical mixtures. Microcrystalline cellulose, titanium dioxide, colloidal silica, ferric oxide, lactose monohydrate, and sodium starch glycolate were compatible, while magnesium stearate, polyethylene glycol (PEG) 8000, Poloxamer 188, and hydroxypropyl methyl cellulose (HPMC) E15 showed incompatibility with the drug. Heat–cool–heat analysis of the physical and the ground mixture of later three excipients showed polymorphic transformation of atovaquone form III to form I, which occurred via amorphization with HPMC E15 and through solubilization mechanism with remaining two excipients. These outcomes were further supported by hot-stage microscopy. Results of milling experiments revealed a milling time-dependent polymorphic transformation and solubilization with HPMC E15 and PEG 8000, respectively. This study highlights the importance of compatibility assessment for selection of excipients in specific unit operations such as milling and grinding.

FABRICATION AND OPTIMIZATION OF NOVEL GLIPIZIDE SUSTAINED RELEASE MATRICES FOR SOLUBILITY AND DISSOLUTION ENHANCEMENT BY SOLID DISPERSION THROUGH HYDROPHILLIC CARRIERS

The present research work was to improve the dissolution rate of glipizide which belongs to BCS II drug by enhancing its aqueous solubility using different hydrophilic carriers like PEG 6000 and hydroxypropyl methylcellulose E15 (HPMC E15). The solid dispersion was embedded into the matrix of polymers to sustain the release pattern of drug. The various solid dispersion formulations were prepared by employing fusion method using different carriers. Further solid dispersion formulations were subjected to different in-vitro evaluation tests for solubility, drug content uniformity, drug-polymer interaction, DSC study and in-vitro drug release study. Tablets were prepared by direct compression method and evaluated for various physical parameters. A direct compression method using response surface methodology, followed by optimization of the evaluated parameters was employed to get the final optimized formulation. The results of drug content uniformity showed the uniform dispersion of glipizide in solid dispersion formulations. The DSC endothermic peak at 216.08°C due to glipizide was partially and completely disappeared in solid dispersion formulation indicating that drug was completely dispersed in formulations. In-vitro drug release showed 80.35% in 60 minutes for the best solid dispersion formulation S3 (ratio 1:3). Among all the formulations, F4 shows 92.87% better sustained release at the end of 12 hrs. The release co-efficient values ‘n’ (E‚0.5) indicated that the drug release followed fickian diffusion mechanism based on formulation factors. The stability studies were carried out according to ICH guideline and result found of selected formulation was stable.Keywords: Glipizide, Solid dispersion, Xanthan gum, MatricesÂ