Methods for Improving the Solubility of Water-Insoluble Drugs:

A Comprehensive Review

 

Wajid Ahmad*, Rihan Sheikh, Razia Ahmad, Suhana Khan

Department of Pharmaceutics, Institute of Pharmacy, Ankara, Turkey.

*Corresponding Author E-mail: wajidahmad806@gmail.com

 

ABSTRACT:

Orally directed medications totally ingest just when they show reasonable dissolvability in gastric medium and such medications shows great bioavailability. The solvency and disintegration properties of medications assume a significant part during the formulation development. Greater part of the disappointments in the new medication improvement have been credited to poor water dissolvability of medication. It is widely accepted that poor water dissolvability is quite possibly the most every now and again experienced troubles in the field of pharmaceutics. Low solvency and ensuing unacceptable disintegration rate regularly bargain oral bioavailability. There are most remedial specialists used to create fundamental impacts by oral course that are the favored method of organization inferable from its few benefits and high quiet consistence contrasted with different courses. Thusly the current methodologies being utilized for BCS class II medications, along with retention enhancers, can be applied to detail class IV compound. Effervescent Assisted Fusion Technique, Solvent Evaporation method, Microemulsion, Liposomes are some imperative methodologies regularly utilized to improve the dissolvability of ineffectively water dissolvable medications. Determination of technique for solvency upgrade relies on drug qualities like dissolvability, substance nature, melting point, retention site, actual nature, pharmacokinetic conduct, etc, measurement structure necessity like tablet or capsule formulation, strength, quick or modified release. This review features the novel strategies accessible for improving solvency, disintegration and bioavailability of medications with poor fluid dissolvability.

 

KEYWORDS: Solubility Enhancement, Drug Release, Nanocrystallization, BCS, Novel Techniques.

 

 


INTRODUCTION:

Dissolvability is the property of solid, liquid or gaseous synthetic substance called solute to disintegrate in a solid, liquid or gaseous dissolvable. The degree of the dissolvability of a substance in a particular dissolvable is estimated as the saturation concentration, where adding more solute doesn't expand the concentration of the solution and starts to precipitate the excess measure of solute.

 

 

 

Solvency is a critical physicochemical factor influencing absorption of medication and its therapeutic viability. Formulation development would prompt be disappointment if drug having poor watery dissolvability. The low disintegration rate and low solvency of medication substances in water in watery G.I.T liquid much of the time prompts lacking bioavailability. The dare to improve the dissolvability and disintegration of hydrophobic medications stay perhaps the trickiest undertaking in drug advancement. A few strategies have been acquainted with win over this issue.1,2

 

Fig 1:- The Extent of Solubility

 

The degree of solvency goes broadly, from boundlessly solvent like ethanol in water, to inadequately dissolvable, like silver chloride in water. The term insoluble is regularly applied to inadequately or ineffectively dissolvable mixtures. Various other graphic terms are likewise used to qualify the degree of solvency for a given application. For instance, U.S. Pharmacopeia gives the accompanying terms:

·       Very solvent: under 1 mass piece of dissolvable needed to disintegrate 1 mass piece of solute.

·       Freely dissolvable: 1-10 mass piece of dissolvable needed to disintegrate 1 mass piece of solute.

·       Soluble: 10-30 mass piece of dissolvable needed to break down 1 mass piece of solute.

·       Sparingly dissolvable: 30-100 mass piece of dissolvable needed to break down 1 mass piece of solute.

·       Slightly dissolvable: 100-1000 mass piece of dissolvable needed to disintegrate 1 mass piece of solute.

·       Very marginally solvent: 1000-10000 mass piece of dissolvable needed to break up 1 mass piece of solute.

·       Practically insoluble or insoluble: 10000 and over mass piece of dissolvable needed to disintegrate 1 mass piece of solute.

 

The water solvency of a medication is a basic property that assumes a significant part in the assimilation of the medication after oral direction. It likewise oversees the chance of parenteral organization of a medication and is helpful in controlling and testing of medication properties during the medication plan and advancement measure. The medication dissolvability is a balance measure yet in addition the disintegration rate at which the strong medication or medication from the dose structure passes into arrangement is fundamentally significant when the disintegration time is limited.3,4 Although the oral bioavailability of a medication relies upon watery solvency, drug penetrability, disintegration rate, first-pass digestion and powerlessness to efflux components, watery dissolvability and medication porousness are additionally significant boundaries ascribed to oral bioavailability.5 In drug disclosure, the quantity of insoluble medication competitors has expanded as of late, with practically 70% of new medication applicants showing helpless water dissolvability6 For these medication up-and-comers, poor fluid dissolvability and helpless disintegration in the GI liquids is a restricting element to the in vivo bioavailability after oral direction. In this manner, in vitro disintegration has been accepted as a significant component in drug improvement and consequently expanding the disintegration pace of inadequately dissolvable medications and upgrading their bioavailability is a significant test to drug scientist.7, 8

 

Effect of Solubility BCS (Biopharmaceutical Classification SSystem):

The Biopharmaceutics Classification System (BCS) has discovered extensive utility in drug disclosure, item improvement and medication item administrative sciences. The order conspire catches the two most huge variables impacting oral medication retention; solvency and intestinal penetrability and it has demonstrated to be an extremely helpful and a broadly acknowledged beginning stage for drug item improvement and medication item guideline. The unthinking base of the BCS approach has, most likely, added to its wide spread acknowledgment and utility. All things considered, under the straightforwardness of BCS are many itemized complication, both in vitro and in vivo which should be assessed and explored for some random medication and medication item. In this original copy we propose a straightforward augmentation of the BCS classes to incorporate subspecification of acid (a), base (b) and neutral (c) for classes II and IV. Sub-arrangement for Classes I and III (high dissolvability tranquilizes as presently characterized) is for the most part not required with the exception of maybe in marginal solvency cases. It is notable that the, pKa actual property of a medication (API) essentially affects the watery dissolvability disintegration of medication from the medication item both in vitro and in vivo for BCS Class II and IV acids and bases, and is the premise, we propose for a sub-characterization expansion of the first BCS arrangement.9,10

 

Enhancement of Solubility and Effect of Enhancement of Solubility on Absorption of Drug:

Dissolvability, the occurance of disintegration of solute in dissolvable to give a homogenous framework, is one of the significant boundaries to accomplish wanted convergence of medication in systemic flow for wanted (expected) pharmacological reaction. Low fluid dissolvability is the serious issue experienced with detailing advancement of new substance elements just as for the conventional turn of events. Any medication to be consumed should be available as in the form of solution at the site of retention. Different strategies are utilized for the upgrade of the solvency of inadequately solvent medications which incorporate physical and compound changes of medication and different techniques like molecule size decrease, precious stone designing, salt arrangement, strong scattering, utilization of surfactant, complexation, etc. Choice of dissolvability improving technique relies upon drug property, site of ingestion, and required measurement structure attributes.

 

The helpless solvency and low disintegration pace of inadequately water dissolvable medications in the watery gastrointestinal fluids frequently cause insufficient bioavailability. Particularly for class II (low dissolvability and high penetrability) substances agreeing to the BCS, the bioavailability might be improved by expanding the dissolvability and disintegration pace of the medication in the gastro- intestinal fluids. With respect to BCS class II medications rate restricting step is drug discharge from the measurement structure and solvency in the gastric fluid and not the assimilation, so expanding the dissolvability thus expands the bioavailability for BCS class II medications.

 

Effect of Solubility Enhancement on Absorption of Drugs:-

Legitimate choice of dissolvability improvement technique is the way to guarantee the objectives of a decent detailing like:

1)   Great oral bioavailability

2)   Reduce recurrence of dosing and better understanding consistence

3)   Low expense of creation

 

Determination of technique for dissolvability improvement relies on drug qualities like solvency, substance nature, melting point, absorption site, actual nature, pharmacokinetic conduct, etc, dose structure prerequisite like tablet or case detailing, strength, quick or altered delivery.11

 

Methods to Enhance Solubility:

1. Effervescent Assisted Fusion Technique:

Effervescent Assisted Fusion Technique for getting solid dispersion is appropriate for drugs which dissolves without singing or disintegrating. Medications having higher dissolving point and inclination to corrupt and it may not be acceptable possibility for this method.

 

Execution:

Precisely weight measures of carrier are set in an aluminum skillet on a hot plate and condense, with consistent mixing, at a temperature of above 600C. A precisely weight measure of active medication is joined into the softened carrier with blending to guarantee homogeneity. The blend is warmed until a reasonable homogeneous dissolve is acquired. The dish is then taken out from the hot plate and permit to cool at room temperature. The actual combination of a medication and a water-dissolvable carrier was warmed straight forwardly until it gets softened. The liquefied combination was then cooled and hardened quickly in an ice shower under thorough blending. The last strong mass was squashed, pounded, and sieved which improve the solvency and bioavailability of medication. Restriction with respect to this strategy is at high temperature many medication may get corrupted.12

 

Synthetic compounds: Mannitol, Citric acid, Sodium bicarbonate, polyethylene glycol, Gelucire, Poloxamer 127.13

 

2. Solvent evaporation method:

In the solvent evaporation method, the medication is disintegrated, scattered, or emulsified into a natural polymer arrangement, which is then emulsified into an outside watery or oil stage. The microspheres are shaped after dissolvable dispersion or dissipation and polymer precipitation.

 

Execution:

In dissolvable vanishing technique we break down both the medication and the transporter in a typical dissolvable and afterward dissipate the dissolvable under vacuum to create a strong arrangement.14 Tachibechi and Nakumara were quick to break down both the medication (β-carotene and the transporter PVP) in a typical dissolvable and afterward vanish the dissolvable under vacuum to deliver a strong scattering. Usually utilize dissolvable like ethanol, chloroform, or a combination of ethanol and dichloromethane. For some situation cosolvant may utilize on the grounds that huge volume of solvents just as warming might be needed to empower total disintegration of medication and transporter. The fundamental benefit of the dissolvable strategy is warm disintegration of medications or transporters can be forestalled in light of the generally low temperatures needed for the dissipation of natural solvents. The impediments of dissolvable strategy, for example, costly, natural, and hard to track down normal and removable solvents, trouble in totally eliminating fluid dissolvable, trouble of recreating gem form.15 Synthetic substances: Dichloromethane, Chloroform, Ethyl acetic acid derivation, Eudragit E100, Eudragit RS, Aceton, and Ethanol.

 

3. Microemulsion:

Microemulsions are clear, steady, isotropic combinations of oil, water and surfactant, often in mix with a cosurfactant. These frameworks are right now important to the drug researcher as a result of their extensive potential to go about as medication conveyance vehicles by joining a wide scope of medication atoms. To see the value in the capability of microemulsions as conveyance vehicles, thermodynamically stable species, with a lot more modest drop width (6 to 80nm) and along these lines are outwardly straightforward or clear. Notwithstanding the fluid stage, oil stage, and surfactant, they have a "cosurfactant," and the extents of the segments are picked with the end goal that they are in a steady district of the particular stage graph; oil content is by and large 2-20% percent. In contrast to ordinary emulsions, microemulsions structure precipitously on blending in with next to zero mechanical energy applied. 16

 

Execution:

1) Phase titration technique:

Attenuation of an oil-surfactant combination with water. [W/O] Attenuation of a water surfactant combination with oil. [O/W]. Blending of all segments on the double, in certain frameworks, the sequence of additives expansion may decide if a microemulsion structures or not.

 

2) Phase reversal technique:

Temperature range in which an o/w microemulsions transforms to a w/o type. Utilizing non surfactants polyoxyethylene are entirely suspectible to temperature with expanding the temperature, the polyoxyethylene bunch gets dried out, adjusting basic pressing boundary which brings about the stage reversal. For ionic surfactants expanding temperature, increment the electrostatic shock between the surfactant headgroups accordingly causing inversion of film curve. Subsequently, the impact of temperature is inverse with the impact seen with nonionic surfactants.

 

Synthetics: Tween 80, Labrasol, Propylene glycol, Isopropyl myristate, Transcutol P.17,18

 

Evaluation Parameters:

1. Micromeretics Property:19,20

a. Angle of Repose:

The angle of repose was controlled by the funnel strategy. The precisely gauged powder was taken in a funnel. The tallness of the funnel was changed so that the tip of the funnel just contacted the zenith of the pile of the granules. The granules were permitted to move through the channel unreservedly onto the surface. The breadth of the powder cone was estimated and point of rest was determined utilizing the accompanying condition.

 

Θ = tan–1(h/r)

 

Where, h and r are the height and radius of the powder pile, individually.

 

b. Bulk Density and Tapped Density:

Bulk thickness and Tapped thickness was resolved. An amount of 2g of powder beforehand delicately shaken to break any agglomerates formed, was brought into a 10 ml estimating chamber. After the underlying volume was noticed, the chamber was permitted to fall under its own load on to a hard surface from the stature of 2.5cm at 2s spans. The tapping was proceeded until no further change in volume was noted. Bulk Density and Tapped Density were determined utilizing the accompanying equations.

 

Bulk Density = Weight of the Powder/Volume of the pressing.

 

Tapped Density  = Weight of the powder/Tapped volume of the pressing

 

c. Compressibility index/carr's index:

The stream property was dictated by estimating the compressibility file. A significant measure can be gotten from the Bulk Density and Tapped Density. As per the hypothesis, the less compressible materials are more flow able. A material having upsides of under 20–30% is characterized as the free streaming material. In view of the Bulk Density and Tapped Density, the rate compressibility of the mass medication was controlled by utilizing the accompanying formula:

 

                                     Tap density – Bulk density

Compressibility Index = -------------------------------x 100

                                                     Tap density

 

d. Hausner's Ratio:

Hausner's Ratio gives a forecast of stream properties identified with between molecule grinding. It is determined utilizing bulk density and tapped density as displayed in Equation. Upsides of Hauner Ratio under 1.25 demonstrate great flowability.

 

Hausner's Ratio = Tapped Density/Bulk Density

 

2. pH-Determination:

1.0gm of powder was taken in test tube and weakened up to 10ml with refined water and checked for pH with pH meter.18,19

 

 

3. Particle Size Analysis:

Particle size investigation was performed by optical microscopy utilizing a compound magnifying instrument. The slide containing test was mounted on the phase of the magnifying lens, and width of in any event 100 particles was estimated utilizing an adjusted visual micrometer. The normal molecule size was controlled by utilizing the Edmondson's condition:21,22

 

Dmean = Σnd/Σn

Where, n= number of particles noticed and d = mean size range.

 

4. Morphological Study:

Scanning Electron Microscopy method is utilized for deciding the surface morphology of the sample. The sample is set up by sprinkling the powder on the tape adhered connected to an aluminum stub. The stubs are covered utilizing the combination of gold and palladium at a thickness of 250–450å under an argon air in a high vacuum evaporator at a voltage of 20 KV, current 10 mA, and low pressing factor. Photomicrographs are assumed the arbitrary screening of tests utilizing Scanning Electron Microscopy.23

 

5. X-Ray Diffraction Method:

The translucent (crystalline) or undefined (amorphous) nature was dictated by X-Ray Diffraction estimation which was done with a X beam diffractometer. From the points and forces of these diffracted radiates, X-beam diffractometer can deliver a three dimensional image of the densities of the electrons inside the gem. Powder - XRD's examination were performed by presenting the samples to CUK-α (copper) radiation (45 kv, 30 mA) and checking from 10 degree to 60 degree and step width of 0.05 degree and sweep speed 10 degree/minute. The instrument measure interlayer dividing d which is determined from the scattering angle theta, utilizing bragg's condition:20

 

nλ= 2d sin ɵ.

Where λ is the frequency of the incident x-beam bar and n is the order interference.

Acquired P-XRD designs were contrasted and the trademark drug top power got for the unadulterated medication, excipients and actual blends.

 

6. Percentage Yield:

To register the percent yield, it is first important to decide the amount of the item ought to be framed dependent on stoichiometry. This is known as the theoretical yield, the most extreme measure of item that could be shaped from the given measures of reactants. The actual yield is the measure of item that is really framed when the response is completed in the lab. The percent yield is the proportion of the actual yield the theoretical yield, communicated as a percentage. The percent yield of every one of the example was determined from the articulation:

 

                         Actual Yield

% Yield = --------------------------*100

                    Theoretical Yield

 

Percent yield is vital in the assembling of items. Percent yields are naturally under 100%. However, percent yields more prominent than 100% are conceivable if the deliberate result of the response contains debasements that cause its mass to be more noteworthy than it really would be if the item was unadulterated.24

 

7. Differential scanning calorimetry (DSC):

Thermal analysis is a significant assessment method to track down any conceivable cooperation between the medication and excipients. Such communication can be recognized by any adjustment of thermogram. Around 1 mg of the sample was fixed in the aluminum container and warmed at the pace of 10°C/min, covering a temperature range of 30°C to 300°C under nitrogen environment of stream rate 20ml/min and Differential Scanning Calorimetry thermogram for unadulterated medication and prepared formulation was acquired. 25

 

8. Drug Content Determination:

The medication content was recognized by scattering 50 mg plan in 10mLorganic dissolvable ethanol, trailed by blending in with an attractive stirrer for 12 h to wet the polymer and to extricate the medication. After filtration through a Whatman filter, the medication fixation in the ethanol stage was resolved spectrophotometrically at their pertinent nm by making the ideal weakening with 0.1N HCl. Every assurance was made in three-fold. The rate drug content are to be determined as follows:23

 

% Drug content = (Weight of medication in sample/Weight of test) × 100

 

9. In vitro drug release study:

In vitro drug release examines were performed with a USP (type 2) disintegration apparatus. Tests of prepared formulation containing 10mg were tested in buffer solution. The rotational speed was set at 30rpm and temperature for the disintegration medium was set at 37ºC. Tests (1mL) were removed at standard time spans and for every withdrawal the relating volume was supplanted with new buffer of a similar temperature. Tests were separated (PTFE O.45μm) and measured spectrophotometrically at specific frequency. Total rate drug discharge was determined utilizing a condition acquired from a standard curve.26,27

 

CONCLUSION:

For orally managed drugs solvency is one of the rate restricting boundary to accomplish their ideal focus in foundational dissemination for pharmacological reaction. Issue of solvency is a significant test for plan researchers. Different epic strategies, portrayed in this survey alone or in mix can be effectively used to upgrade the dissolvability of hydrophobic medications for improving their oral bioavailability, however fruitful improvement is predominantly relies upon choice of technique. Among all the dissolvability upgrade strategies. Bubbly Assisted Fusion Technique, Solvent Evaporation strategy, Micro emulsion these are the most alluring strategies to determine the dissolvability issues of hydrophobic medications

 

REFERENCES:

1.      Sharma D, Soni M, Kumar S, Gupta GD. Solubility enhancement–eminent role in poorly soluble drugs. Research Journal of Pharmacy and Technology. 2009;2(2):220-4.

2.      Malviya VR, Tawar MG. Preparation and Evaluation of Oral Dispersible Strips of Teneligliptin Hydrobromide for Treatment of Diabetes Mellitus. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 Jan 31;13(1):4745-52.

3.      Jadhav YL, Parashar B, Ostwal PP, Jain MS. Solid dispersion: Solubility enhancement for poorly water soluble drug. Research Journal of Pharmacy and Technology. 2012;5(2):190-7.

4.      Malviya V, Ladhake V, Gajbiye K, Satao J, Tawar M. Design and Characterization of Phase Transition System of Zolmitriptan Hydrochloride for Nasal Drug Delivery System. International Journal of Pharmaceutical Sciences and Nanotechnology. 2020 May 31;13(3):4942-51.

5.      Chauhan NN, Patel NV, Suthar SJ, Patel JK, Patel MP. Micronization of BCS Class–II Drugs by Various Approaches for Solubility Enhancement–A Review. Research Journal of Pharmacy and Technology. 2012;5(8):999-1005.

6.      Malviya VR, Pande SD. Road CKN. Preparation ad Evaluation of Zolmitriptan Hydrochloride Lozenge. J Pharma Res. 2019;8(8):624-9.

7.      Jagtap VA, Talele AN, Bendale AR, Narkhede S, Jadhav A, Vidyasagar G. Solubility Enhancement of Pioglitazone by Using Poloxamer (188 and 407) with the Help of Kneading Method. Research Journal of Pharmacy and Technology. 2010;3(4):1152-7.

8.      Gubbi S, Jarag R. Liquisolid technique for enhancement of dissolution properties of bromhexine hydrochloride. Research Journal of Pharmacy and Technology. 2009;2(2):382-6.

9.      Malviya VR, Pande SD, Bobade NN. Preparation and Evaluation of Sustained Release Beads of Zolmitriptan Hydrochloride. Research Journal of Pharmacy and Technology. 2019;12(12):5972-6.

10.   Chitlange SS, Pawbake GR, Pandkar SV, Wankhede SB. Formulation and evaluation of diacerein solid dispersion for solubility and dissolution rate enhancement. Research Journal of Pharmacy and Technology. 2011;4(6):932-7.

11.   Malviya V, Manekar S. Design, Development and Evaluation of Aceclofenac and Curcumin Agglomerates by Crystallo Co-Agglomeration Technique. Research Journal of Pharmacy and Technology. 2021 Mar 1;14(3):1535-41.

12.   Malviya V, Thakur Y, Gudadhe SS, Tawar M. Formulation and evaluation of natural gum based fast dissolving tablet of Meclizine hydrochloride by using 3 factorial design 2. Asian Journal of Pharmacy and Pharmacology. 2020;6(2):94-100.

13.   Srikanth MV, Babu GV, Sunil SA, Rao NS, Kumar KP, Murthy KV. Studies on the effect of hydrophilic carriers in the dissolution rate enhancement of poorly soluble drug, bicalutamide. Research Journal of Pharmacy and Technology. 2010;3(2):592-5.

14.   Mishra R, Gautam SS, Prasad RK, Patel AK, Sahu AK. Solubility enhancement of clarithromycin using solid dispersion and effervescence assisted fusion technique. Research Journal of Pharmacy and Technology. 2016;9(6):677-86.

15.   Malviya V. Preparation and Evaluation of Emulsomes as a Drug Delivery System for Bifonazole. Indian journal of pharmaceutical education and research. 2021 Jan 1;55(1):86-94.

16.   Malviya V, Pande S. Development and Evaluation of Fast dissolving Film of Fluoxetine hydrochloride. Research Journal of Pharmacy and Technology. 2021 Oct 31;14(10):5345-50.

17.   Eskandar Moghimipour, Anayatollah Salimi, Fatemeh Leis, Preparation and evaluation of tretinoin microemulsion based on pseudo- ternary phase digram. Adv Pharm Bull. 2012 Dec; 2(2): 141-147

18.   Francis Szoka, Jr., Demetrios Papahadjopoulos, Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse phase evaporation, 9th ed, PNAS, Vol. 75, September 1978, pp. 4194-4198.

19.   Kumar, Vinod, VK Damini, K. Eswar, Kadiri Rajesh Reddy, and P. Sucharitha. "SOMES: A Review on Composition, Formulation Methods and Evaluation of different types of “SOMES” Drug delivery system." International Journal of Applied Pharmaceutics (2020): 7-18.

20.   Satyavathi, K., P. Bhojaraju, M. Srikranthi, and P. Sudhakar. "Formulation and In-Vitro Evaluation of Liposomal Drug Delivery System Of Cabazitaxel." J Pharm Drug Delivery Res 4 (2015): 2.

21.   Malviya V. Design and Characterization of Thermosensitive Mucoadhesive Nasal Gel for Meclizine Hydrochloride. International Journal of Pharmaceutical Sciences and Nanotechnology. 2022 Feb 28;15(1):5782-93.

22.   Kamra, Manju, Anupama Diwan, and Satish Sardana. "Novel Topical Liposomal Gel of Benzoyl Peroxide and Resveratrol for Treatment of Acne."2nded, Asian Journal of Pharmaceutical Research and Development 6, (2018): 27-42.

23.   Burange PJ, Tawar MG, Bairagi RA, Malviya VR, Sahu VK, Shewatkar SN, Sawarkar RA, Mamurkar RR. Synthesis of silver nanoparticles by using Aloe vera and Thuja orientalis leaves extract and their biological activity: a comprehensive review. Bulletin of the National Research Centre. 2021 Dec;45(1):1-3.

24.   Asif, Hussain Mohammed, Renukuntla Arun Kumar, T. Rama Rao, and M. A. Anjum. "Preparation and Evaluation OfEthylcellulose Microspheres Prepared By Solvent Evaporation Technique." 7thed, Int. J. Pharm. Pharma. Sci 6, (2014): 264-266.

25.   PYadav VI, Jadhav PR, Kanase KI, Bodhe AN, Dombe SH. Preparation and Evaluation of Microemulsion Containing Antihypertensive Drug." 5thed, Int. J. Appl. Pharm 10, (2018).

26.   Malviya V, Burange P, Thakur Y, Tawar M. Enhancement of Solubility and Dissolution Rate of Atazanavir Sulfate by Nanocrystallization. Indian Journal of Pharmaceutical Education and Research. 2021 Jul 1;55(3):S672-80.

27.   Malviya, Vedanshu, Mukund Tawar, Prashant Burange, and Rahul Jodh. "A Brief Review on Resveratrol." (2022): 157-162.

 

 

 

 

 

 

Received on 09.03.2022         Modified on 14.06.2022

Accepted on 01.08.2022   ©AandV Publications All Right Reserved

Res.  J. Pharma. Dosage Forms and Tech.2022; 14(4):309-314.

DOI: 10.52711/0975-4377.2022.00051