Structure based release kinetics analysis of doxazosin mesylate sustained-release tablets using micro-computed tomography

The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping test.With their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release kinetics.The structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic structures.Furthermore,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic preparations.Moreover,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%ethanol.In conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.

Effects of Silicon Formulations on Cold Tolerance of Rice Seedlings

To investigate the effects of silicon formulations on the cold tolerance of rice seedlings,Song Japonica 16(not cold tolerant)and Dongnong 427(cold tolerant)rice varieties were used as test materials and four different types of silicon formulations,Si-50-G,Si-60-G,Si-T-G,and Si-E-G,were applied as foliar sprays at the seedling stage,and a control group CK(equal amount of distilled water)was set up.One week after the first silicon spray,two types of rice were subjected to low-temperature stress treatments at day/night temperatures of 12℃/10℃for 2,4,6,and 8 days.The effects of different silicon formulations on the chlorophyll,proline(Pro)and soluble sugar contents as well as superoxide dismutase(SOD),peroxidase(POD)and catalase(CAT)activities of rice seedlings under low-temperature stress were compared to find out the effects of silicon formulations on the cold tolerance of rice seedlings.The results showed that silicon formulations could significantly increase the chlorophyll content of rice seedling leaves,with Si-50-G being the most effective,with a significant increment of 40.17%compared to the CK at 2 days of low temperature.Four silicon formulations significantly increased the proline content and soluble sugar content of rice leaves at low temperature for 4-8 days.For Song Japonica 16,the most significant increment in leaf POD activity was observed in Si-E-G treatment at 2,4 and 8 days of temperature stress,with 73.58%,20.95%and 217.24%increases compared to the CK,respectively.For 4 and 6 days of temperature stress,the most significant increase in CAT activity was observed in Si-E-G treatment,with 25.70%and 75.78%increases compared to the CK,respectively.For Dongnong 427,the Si-60-G treatment showed the highest increase in leaf SOD activity for 4 and 8 days of temperature stress,with significant increases of 58.15%and 82.76%compared to the CK,respectively,and the Si-E-G treatment showed the highest increase in leaf POD activity for 2 and 8 days of temperature stress,with significant increases of 97.75%and 245.10%compared to the CK,respectively.It showed that the spraying of silicon formulations could significantly enhance the cold tolerance of rice.This study provided a scientific basis for the rational use of silicon formulations to enhance cold tolerance in rice and had important theoretical and practical significance for ensuring sustainable high and stable rice yields in Heilongjiang Province,as well as for the development of silicon fertilizers.

Formulations of traditional Chinese medicine for the prevention and treatment of radiationinduced injury

The likelihood of radiation-induced injury(RII)has increased.Currently,the chemical drugs used to prevent and control radiation damage have some drawbacks,such as high toxicity,which can also have other side effects on the body.However,many traditional Chinese medicine(TCM)monomers,single TCM,and compound TCM preparations have shown good therapeutic effects against radiation damage with increased safety and minimal adverse reactions.Therefore,new anti-RII TCMs must be explored and developed.This study reviewed the TCM preparations for the prevention and treatment of RII and their mechanisms of action to provide a better theoretical basis for research on the prevention and treatment of RII.TCM is an efficient,safe,and convenient strategy for the prevention and treatment of RII.

Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers

Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.

Preparation of Sustained-release Silybin Microspheres by Spherical Crystallization Technique

Aim To improve the dissolution rate and bioavailability of silybin. Methods Sustained-release silybin microspheres were prepared by the spherical crystallization technique with soliddispersing and release-retarding polymers. A differential scanning calorimeter and an X-ray diffractometer were used to investigate the dispersion state of silybin in the microspheres. The shape, surface morphology, and internal structure of the microspheres were observed using a scanning electron microscope. Characterization of the microspheres, such as average diameter, size distribution and bulk density of the microspheres was investigated. Results The particle size of the microspheres was determined mainly by the agitation speed. The dissolution rate of silybin from microspheres was enhanced by increasing the amount of the dispersing agents, and sustained by the retarding agents. The release rate of microspheres was controlled by adjusting the combination ratio of the dispersing agents to the retarding agents. The resuits of X-ray diffraction and differential scanning calorimetry analysis indicated that silybin was highly dispersed in the microspheres in amorphous state. The release profiles and content did not change after a three-month accelerated stability test at 40 ℃ and 75% relative humidity. Conclusion Sustained-release silybin microspheres with a solid dispersion structure were prepared successfully in one step by a spherical crystallization technique combined with solid dispersion technique. The preparation process is simple, reproducible and inexpensive. The method is efficient for designing sustained-release microspheres with water-insoluble drugs.

Pharmacokinetics and Relative Bioavailability ofsustained-release Tablets of Diclofenac Sodiumin Male Volunteers

The pharmacokinetics of a sustained- release formulation and an enteric- coated tablet of diclofenac sodium were studied on 8 healthy male volunteers in an open,randomized crossover study.Drug level in serum was assayed by HPLC method.The changes in serum concentration were conformed to a l-compartment open model.The t_1/2 (Ke)averaged 2.15±0.17 and ll.60 ± l.95 h,and the areas under the drug concentration curves were 5.87 ± 0.67 and 5.55 ± 0.57μgh/ml for enteric-coated and sustained-release tablet of diclofenac sodium,respectively. The mean relative bioavailability of sustained-release tablet was 0.95 to that of enteric-coated tablet.

Complex formulations, simple techniques: Can 3D printing technology be the Midas touch in pharmaceutical industry?

3 D printing is a method of rapid prototyping and manufacturing in which materials are deposited onto one another in layers to produce a three-dimensional object. Although 3 D printing was developed in the 1980 s and the technology has found widespread industrial applications for production from automotive parts to machine tools,its application in pharmaceutical area is still limited. However,the potential of 3 D printing in the pharmaceutical industry is now being recognized. The ability of 3 D printing to produce medications to exact specifications tailored to the needs of individual patients has indicated the possibility of developing personalized medicines. The technology allows dosage forms to be precisely printed in various shapes,sizes and textures that are difficult to produce using traditional techniques. However,there are various challenges associated with the proper application of3 D printing in the pharmaceutical sector which should be overcome to exploit the scope of this technology. In this review,an overview is provided on the various 3 D printing technologies used in fabrication of complex dosage forms along with their feasibility and limitations.

Preparation of dry flowable formulations of Clonostachys rosea by spray drying and application for Sclerotinia sclerotiorum control

A dry flowable formulation of Clonostachys rosea with fungicidal activity against Sclerotinia sclerotiorum was prepared by spray drying. The formulation was optimized by a four-factor, three-level orthogonal experiment to screen inert ingredients and spray-drying conditions. The optimal dry flowable formulation of C. rosea included 30% C. rosea （ratio of conidia powder and its fermentation broth is 1：3）, 3% Morwet EFW, 4% K12, 10% Morwet D425, 9% sodium salt of polynaphthalene sulphonic acid （NNO）, 5% croscarmellose sodium, 5% （NH4）2SO4, 0.5% carboxymethyl cellulose sodium （CMC-Na）, 1% oxalic acid and palygorskite （carrier） up to 100%. The formulation exhibited good physical characteristics, such as high dispersibility, viability and a long shelf life. Plate antagonism tests and pot trials indicated that the dry flowable formulation was very effective against S. sclerotiorum, with control efficiency of up to 88.30%. This dry flowable formulation of C. rosea is a new potential commercial fungicide for spray drying to control S. sclerotiorum.

Predicting oral disintegrating tablet formulations by neural network techniques

Oral disintegrating tablets(ODTs) are a novel dosage form that can be dissolved on thetongue within 3 min or less especially for geriatric and pediatric patients. Current ODT for-mulation studies usually rely on the personal experience of pharmaceutical experts andtrial-and-error in the laboratory, which is inefficient and time-consuming. The aim of cur-rent research was to establish the prediction model of ODT formulations with direct com-pression process by artificial neural network(ANN) and deep neural network(DNN) tech-niques. 145 formulation data were extracted from Web of Science. All datasets were dividedinto three parts: training set(105 data), validation set(20) and testing set(20). ANN andDNN were compared for the prediction of the disintegrating time. The accuracy of the ANNmodel have reached 85.60%, 80.00% and 75.00% on the training set, validation set and testingset respectively, whereas that of the DNN model were 85.60%, 85.00% and 80.00%, respec-tively. Compared with the ANN, DNN showed the better prediction for ODT formulations.It is the first time that deep neural network with the improved dataset selection algorithmis applied to formulation prediction on small data. The proposed predictive approach couldevaluate the critical parameters about quality control of formulation, and guide researchand process development. The implementation of this prediction model could effectivelyreduce drug product development timeline and material usage, and proactively facilitatethe development of a robust drug product.

Estimation of boswellic acids in herbal formulations containing Boswellia serrata extract and comprehensive characterization of secondary metabolites using UPLC-Q-Tof-MS^e

Boswellia serrata is a widely used herb in Indian systems of medicine and is well known for its potential medicinal properties.A chromatographic method was developed for the analysis and quanti cation of six boswellic acid marker compounds,i.e.,keto boswellic acid(1),3-O-Acetyl 11-keto-boswellic acid(2),-b Boswellic acid(3),-Boswellic acid(4),3-O-Acetyl--boswellic acid(5)and 3-O-Acetyl--boswellic acid b(6)in commercial herbal products containing B.serrata as an ingredient.Combining UPLCbwith Q-Tof-MS/MS makes the better identi cation of secondary metabolites and adulterants in the herbal formulations containing B.serrata in rapid time using fragmentation approach than the traditional approaches.In this study quanti cation of boswellic acids with UPLC-PDA method was performed as per the pharmacopeia guidelines.Furthermore,minor phytochemical constituenBoswellia serrata is a widely used herb in Indian systems of medicine and is well known for its potential medicinal properties.A chromatographic method was developed for the analysis and quantification of six boswellic acid marker compounds,i.e.,keto boswellic acid(1),3-O-Acetyl 11-keto b-boswellic acid(2),ɑ-Boswellic acid(3),b-Boswellic acid(4),3-O-Acetyl-ɑ-boswellic acid(5)and 3-O-Acetyl-b-boswellic acid(6)in commercial herbal products containing B.serrata as an ingredient.Combining UPLC with Q-Tof-MS/MS makes the better identification of secondary metabolites and adulterants in the herbal formulations containing B.serrata in rapid time using fragmentation approach than the traditional approaches.In this study quantification of boswellic acids with UPLC-PDA method was performed as per the pharmacopeia guidelines.Furthermore,minor phytochemical constituents were identified and characterized with the help of LC-Q-Tof-MS/MS fragmentation data and various isoforms of boswellic acids and tirucallic acids in B.serrata oleo-gum-resin extract were identified.ts were identi ed and characterized with the help of LC-Q-Tof-MS/MS fragmentation data and various isoforms of boswellic acids and tirucallic acids in B.serrata oleo-gum-resin extract were identi ed.

A Systemic Review on Topical Marketed Formulations, Natural Products, and Oral Supplements to Prevent Androgenic Alopecia: A Review

Androgens have an intense consequence on the human scalp and body hair.Scalp hair sprouts fundamentally in awol of androgens whereas the body hair hike is vulnerable to the activity of androgens.Androgenetic alopecia(AGA)invoked as males emulate Alopecia due to the cause of the dynamic reduction of scalp hair.Androgens are medium of terminus growth of hair although the body.Local and system androgens convert the extensive terminal follicles into lesser vellus like structure.The out start of this type of alopecia is intensely irregular and the reason behind this existence of enough circulating steroidal hormones androgens and due to genetic predisposition.Effective treatments are available in the market as well as under clinical and preclinical testing.Many herbal formulations are also available but not FDA approved.Different conventional and NDDS formulations are already available in the market.To avoid various systemic side effects of both Finasteride and Minoxidil,topical formulations and natural products(nutrients,minerals,vitamins)now a days are being widely used to treat Androgenic alopecia.CAM(complementary and alternative medicine)provides the option to elect favorable,low-risk,adjuvant and alternative therapies.Herein,we offer a widespread review of topical marketed formulations,natural products,and CAM treatment options for AGA.

Nutritional Evaluation of Complementary Food Formulations from Maize, Soybean and Peanut Fortified with <i>Moringa oleifera</i>Leaf Powder

Nutritional evaluation of complementary food formulations from maize, soybean and peanut fortified with Moringa oleifera leaf powder was carried out. Maize, soybean and peanut were blended in a ratio of 60:30:10 to produce a complementary food, which was then fortified. While the unfortified food product (sample A) served as control, the other three formulations were fortified with 5%, 10% and 15% Moringa leaf powder to give three samples (B, C and D respectively) of fortified food. Nutritional composition determination and feeding trials were then carried out, using two weeks old male albino rats to determine the performance of the food formulations. While the crude protein, crude fibre, and ash contents of the diets increased significantly (p with fortification, with values ranging from 16.04% to 17.59%, 2.25% to 4.42% and 1.40% to 2.50% respectively, crude fat and carbohydrate decreased significantly (p < 0.05), with concomitant decrease in energy, with values ranging from 23.48% to 20.80%, 49.32% to 47.63% and 472.76% to 448.08 kcal/100g respectively in samples A to D. PER values significantly (p < 0.05) improved up to 10% substitution, from 1.77 in unfortified (sample A) to 1.90 in 10% fortified (sample C), but declined at 15% substitution (sample D) to 1.69. Similarly, NPR values increased from 0.71 to 0.76 and 0.68. However, all the PER values including that of Nestle Cerelac (2.04) were lower than, though within the same range, with the value of 2.10 recommended by the Protein Advisory Group (PAG) for complementary foods. Sample C (10% Moringa flour blend) gave the best performance after rat feeding trials.

Development of liposomal formulations: From concept to clinical investigations

Liposome is one of the most successful drug delivery systems applying nanotechnology topotentiate the therapeutic efficacy and reduce toxicities of conventional medicines. Sincethe first doxorubicin-loaded liposome reached the market, numerous researches have beencarried out to develop new liposomal formulations over the past decade and have givenbirth to a series of commercial products. Therapeutic agents, most of which are anti-cancerdrugs, are encapsulated in the aqueous core or lipid bilayers of liposomes to improve theirdelivery to the targeted tissue. There are several liposomal formulations, such as EndoTAG-1 (paclitaxel-loaded cationic liposomes), Lipoplatin (cisplatin-loaded long circulating liposomes) and Stimuvax (a cancer vaccine), showing promising therapeutic value in clinicalstudies. Besides, new designs including environmentally sensitive liposomes, liposomaldrug combinations and liposomal vaccines are now tested in clinical trials.

Birkhoffian Formulations of Bessel Equation

The Birkhoffian mechanics is more general than the Hamilton mechanics,but only some dynamical systems can be realized as a Birkhoffian formulation.This paper proposes a novel Birkhoffian formulation for the classical Bessel equation.Based on the first method of Santilli,the Birkhoffian formulation of Bessel equation is established under the assumption that the Birkhoffian describes the total physical energy of the corresponding conservative systems.Zero and n-th order classical Bessel equations are studied to verify the effectiveness of the proposed formulation.

Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.

Properties of Aroma Sustained-release Cotton Fabric with Rose Fragrance Nanocapsule

The aroma sustained-release cotton fabric was prepared by finishing rose fragrance nanocapsules directly on cotton.The structure and properties of nanocapsules were demonstrated by transmission electron microscope(TEM),dynamic light scattering(DLS),fourier transform infrared spectrometer(FTIR),X-ray diffraction (XRD),gas chromatography-mass spectrometry(GC-MS)and electronic nose.The results showed that the spherical nanocapsule dispersed evenly and the average diameter kept 51.4 nm.The existence of COO peak(1741 cm? 1)in the FTIR curve of the finished cotton fabric and the decrease of crystallinity demonstrated that rose fragrance nanocapsules have been incorporated into the cotton fabrics.The washing resistance of the cotton fabrics finished by 51.4 nm nanocapsules was much better than that by rose fragrance alone.Besides,the loss of fragrance from the cotton fabrics finished by 51.4 nm nanocapsules was obviously lower than that by 532 nm nanocapsules and rose fragrance.The smaller the nanocapsule size,the better the sustained release property.Electronic nose analysis also displayed that the aroma released from the cotton fabrics finished by nanocapsules after washing has no obvious variety in contrast to that without washing.The cotton fabrics finished by nanocapsules has the excellent sustained release property.

Detection and determination of undeclared synthetic caffeine in weight loss formulations using HPLC-DAD and UHPLC-MS/MS

Caffeine is present in products marketed for weight loss, with the purpose of increasing thermogenesis and lipid metabolism. The dosage declared by the product manufacturer, or even its presence, is not always correctly described on the label. This work aimed to investigate the undeclared synthetic caffeine in weight loss formulations by a high-performance liquid chromatography with diode array detection(HPLC-DAD) method. From one hundred products purchased through Brazilian e-commerce, seventeen contained caffeine, either naturally or synthetically added to formulation. The caffeine-containing samples were confirmed by an ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method, and adulteration was clearly proven in five products. The content highest caffeine contained 448.8 mg per dose. Other irregularities were also found; nevertheless, the most serious was the addition of synthetic drugs without asking the consumers. Additional drugs expose the consumer to more possible side-effects as well as deleterious drug interactions. Intentional adulteration with any unlabeled substance is typically motivated by a desire to increase or alter the claimed effect of the marketed product to gain a commercial advantage.

Quality of compounded topical 2% diltiazem hydrochloride formulations for anal fissure

AIM:To investigate the quality of topical 2%diltiazem formulations extemporaneously compounded by retail pharmacies openly offering drug-compounding services.METHODS:A participating healthcare professional wrote 12 prescriptions for compounded 2%diltiazem cream,with 2 refills allowed per prescription.The 12sets of prescriptions were filled,at intervals of 1-2 wk between refills,at 12 different independent retail pharmacies that openly offer drug-compounding services in a major metropolitan region.The 36 resultant preparations,provided as jars or tubes,were shipped,as soon as each was filled,at ambient temperature to the study core laboratory for high-performance liquid chromatography(HPLC)analysis,within 10 d of receipt.For the HPLC analysis,8 different samples of the topical diltiazem,each approximately 1 g in weight,were taken from prespecified locations within each container.To initiate the HPLC analysis,each sample was transferredto a 100 mL volumetric flask,to which methanol was added.The HPLC analysis was conducted in accordance with the laboratory-validated method for diltiazem in cream,ointment,and gel formulations.The main outcome measures were potency(percentage of label claim)and content uniformity of the compounded topical 2%diltiazem formulations.RESULTS:Of the 36 prescriptions filled,30 were packaged in jars and 6 were packaged as tubes.The prescriptions were specifically for cream formulations,but6 of the 12 pharmacies compounded 2%diltiazem as an ointment;for another pharmacy,which had inadequate labeling,the dosage form was unknown.The United States Pharmacopoeia(USP)standard for potency is 90%-115%of label claim.Of the 36 preparations,5(13.89%)were suprapotent and 13(36.11%)were subpotent.The suprapotent prescriptions ranged in potency from 117.2%to 128.5%of label claim,and the subpotent prescriptions ranged in potency from34.8%to 89.8%of label claim.Fourteen(38.9%)preparations lacked content uniformity according to the USP standard of 90%-110%potency and<6%relative standard deviation.Of the 30 formulations packaged in jars,12(40%)lacked content uniformity,while of the6 formulations packaged in tubes,2(33.3%)lacked content uniformity.Nine of the 12 pharmacies(75%)failed USP potency or content-uniformity specifications for at least 1 of the 3 prescription fills.For 5 of the 12pharmacies(41.7%),the mean potency across all three prescription fills was<90%of label claim.CONCLUSION:Patients prescribed topical 2%diltiazem for treatment of anal fissure frequently receive compounded formulations that are misbranded with respect to potency and that lack content uniformity.

Simultaneous Quantification of Ibuprofen and Paracetamol in Tablet Formulations Using Transmission Fourier Transform Infrared Spectroscopy

A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy in tablet formulations for routine quality control laboratories. For the determination of the active pharmaceutical ingredients (API), KBr pellets containing known amount of standards and samples were used for acquisition of the FTIR spectra. The partial least squares (PLS) calibration model was developed using the spectral region from 1781 - 1683 cm-1 for IBP and 1630 - 1530 cm-1 for PC. The excellent coefficients of determination (R2), 0.9999 and 0.9998 were achieved for IBP and PC, respectively. The accuracy of calibration model was also verified through root mean square error of cross validation (RMSECV) which was found to be 0.064. This work clearly shows the capability of transmission FTIR spectroscopy for assessment of exact quantity of API to control the quality of finished products as well as during processing in pharmaceutical industries without involvement of any solvent.

THEORETICAL BASIS AND GENERAL OPTIMAL FORMULATIONS OF ISOPARAMETRIC GENERALIZED HYBRID/MIXED ELEMENT MODEL FOR IMPROVED STRESS ANALYSIS

By the modified three-field Hu-Washizu principle, this paper establishes a theoretical founda- tion and general convenient formulations to generate convergent stable generalized hybrid/mixed cle- ment (GH/ME) model which is invariant with respect to coordinate, insensitive to geometric distortion and suitable for improved stress computation. In the two proposed formulations, the stress equilibrium and orthogonality constraints are imposed through incompatible displacement and internal strain modes respectively. The proposed model by the general formulations in this paper is characterized by including as- sumed stress/strain, assumed stress, variable-node, singular, compatible and incompatible GH/ME models. When using regular meshes or the constant values of the isoparametric Jacobian Det in the assumed strain in- terpolation, the incompatible GH/ME model degenerates to the hybrid/mixed element model. Both general and concrete guidelines for the optimal selection of element shape functions are suggested. By means of the GH/ME theory in this paper, a family of new GH/ME can be and have been easily constructed. The software can also be developed conveniently because all the standard subroutines for the corresponding isoparametric displacement elements can be utilized directly.