INTRODUCTION:

Oral route of administration is considered as the regular chosen method for administering dosage forms because of the convenience and patient compliance. The challenging factors in formulating them includes poor solubility or poor membrane permeability of Active pharmaceutical ingredient (API).

If an API has poor solubility and categorized as Biopharmaceutical Classification System (BCS) class II or IV drug, the dosage form containing those API would not be soluble in biological and gastrointestinal fluids which effects the drug dissolution and further absorption/bioavailability.¹ The solubility improvement techniques should be considered for designing these dosage forms comprising poorly soluble drugs. Solid dispersion (SD) includes the process of dispersing a poorly water soluble API in highly water soluble inert polymeric carriers by different methods like fusion, solvent evaporation, kneading etc. The carrier selection plays a key role in influencing and improving the solubility-dissolution of an API.² The carriers used in formulation are categorized into 3 generations based on their properties, the common examples includes urea, mannitol, sugars, polyethylene glycols, hydroxyl propyl methylcellulose, Gelucire of different grades, polaxomers, etc. In solid dispersions the solubility is increased by different mechanisms like reduction of the particle size, the API is converted partially or completely into amorphous state with reduced crystallinity and improved solubility, wetting is improved due to dispersion in hydrophilic carrier. Pitavastatin calcium is a statin derivative which inhibits an endogenous/internal cholesterol production in the liver. It precisely inhibits and hinders the enzyme Hydroxy methyl glutaryl-coenzyme - A (HMG-CoA) Reductase which plays a key role in converting HMG – CoA to mevalonate derivative which is mevalonic acid. This conversion is regarded as rate-limiting step in cholesterol production. These statins are suggested as one of the frequently recommended treatment for hypercholesterolemia, hyper-lipoproteinemia and hypertriglyceridemia. Pitavastatin is considered as BCS class II drug with low solubility and high permeability features.² The present research aims to formulate and characterize the solid dispersions of Pitavastatin which further helps in improving its solubility and dissolution. The methods of formulation includes fusion and kneading by using second generation carriers like PVP K30, PEG 6000 and Beta Cyclodextrin in different ratios. The prepared SD were evaluated for various properties for future development of tablets.

MATERIALS AND METHODS:

Preformulation Studies: Preformulation study is the first step in rational formulation development of dosage form.³ Pitavastatin Preformulation studies were performed which includes determination of organoleptic properties, micromeritic properties, solubility, melting point, UV spectroscopic method development to determine λ max in different media, construction of standard graph, FTIR, XRD, DSC studies, compatibility studies.

Preparation of solid dispersions:

Materials: Pitavastatin calcium was obtained from Solara active Pharma, Industrial Complex, Tamil Nadu - India. Polyvinylpyrrolidone K30 (PVP K30), Polyethylene Glycol 6000 (PEG-6000), Beta-cyclodextrin was obtained from sigma-Aldrich, Loba chemie and research lab fine Chem industries, Mumbai. The other reagents and chemicals were obtained from Sigma-Aldrich and research lab fine Chem industries, which are of pharmaceutical grade. All other solvents were purchased from SD fine chem. Ltd. Which are of analytical grade. Distilled water was used throughout the research for all the analytical studies. The formulation is presented in table 1. Polyethylene glycol 6000 is non-toxic, odorless, neutral, lubricating, nonvolatile and nonirritating carrier and are used in a variety of pharmaceuticals. The low molecular weight compounds up to 700 are colorless, odorless viscous liquids while polymerized compounds with higher molecular weight than 1,000 are wax like solids. PVP K-30 carrier is a hygroscopic, amorphous polymer, which is a linear nonionic polymer and are soluble in water and organic solvents with pH stability. PVP K-30 forms hard glossy transparent films and have adhesive, cohesive and dispersive properties. Beta cyclodextrin is a carrier with outer surface of molecule is being hydrophilic due to the presence of hydroxyl groups, whereas the inner cavity is hydrophobic, which allows it to interact with and encapsulate hydrophobic molecules.⁴

Table 1: Formulation of solid dispersions of Pitavastatin calcium

S. No.

Formulation code

Composition

Drug: carrier ratio

Method name

PSD1

PSD2

PSD3

PSD4

Pitavastatin Calcium: PEG 6000

1:1

1:2

1:4

1:6

Fusion method

PSD5

PSD6

PSD7

PSD8

Pitavastatin Calcium: Beta Cyclodextrin

1:1

1:2

1:4

1:6

Fusion method

10.

11.

12.

PSD9

PSD10

PSD11

PSD12

Pitavastatin Calcium: PVP K30

1:1

1:2

1:4

1:6

Fusion method

13.

14.

15.

16.

PSD13

PSD14

PSD15

PSD16

Pitavastatin Calcium: PEG 6000

1:1

1:2

1:4

1:6

Kneading method

17.

18.

19.

20.

PSD17

PSD18

PSD19

PSD20

Pitavastatin Calcium: Beta Cyclodextrin

1:1

1:2

1:4

1:6

Kneading method

21.

22.

23.

24.

PSD21

PSD22

PSD23

PSD24

Pitavastatin Calcium: PVP K30

1:1

1:2

1:4

1:6

Kneading method

Preparation of solid dispersions:

Fusion method: Pitavastatin calcium solid dispersions were prepared by using PEG 6000, PVP K30 and Beta cyclodextrin in different ratios of 1:1, 1:2, 1:4 and 1:6 of drug: polymer. The carriers and drug were melted in different ratios which is presented in table 1. Initially, the carrier was heated until melting was attained followed by addition of drug with continuous stirring for few minutes⁵. The melting temperature was adjusted according to the melting point of each carrier used in the formulation which is not similar for all the carriers, for PEG 6000 formulation the melting temperature was 70°C, for PVP K30 and Beta cyclodextrin the temperature was higher than 70°C The molten homogenous mixture produced was cooled immediately on chilled ice bath. Then it was dried and powdered in a mortar and sieved followed by stored in desiccator for future usage. A modification of above method was used for PVP K30, where small quantity of water was added to carrier and heated, the drug was dispersed in heated mixture with stirring then mixture was cooled on chilled ice bath.⁶ The dried mass was crushed, sieved and stored further.

Kneading method:

In this method the carrier was initially wetted with little quantity of ethanol as solvent, then the drug was added and kneaded meticulously for 45minutes.⁷ The homogenous mixture was produced with paste like consistency. It was dried in hot air oven at temperature of 40°C for duration until dry solid dispersion powder was formed. The dried mass was milled and passed through screen followed by and stored in desiccator for future usage.

Preparation of Physical Mixture:

The drug pitavastatin calcium and carriers PEG 6000, PVP K30 and Beta cyclodextrin were weighed in required 1:1 ratio and mixed thoroughly in motor to produce a uniform physical mixture. The mixture helps to analyze the compatibility by FTIR spectral analysis and also by physical observation method.⁸

Characterization and evaluation of Pitavastatin calcium solid dispersions:

Preformulation studies:

Pitavastatin Preformulation studies were performed for determination of organoleptic properties, micromeritic properties, solubility, melting point, UV spectroscopic method development for establishing λ max in different media, standard graph preparation, FTIR, XRD, DSC studies, compatibility studies.⁹

Practical percentage yield:

The yield was determined by weighing the prepared solid dispersions of Pitavastatin Calcium along with considering the individual weights of drug and carrier used in preparation.¹⁰

Weight of prepared solid dispersion

Percentage yield = ––––––––––––––––––––––––––––– × 100

Weight of drug and carrier used

Drug content:

The solid dispersions comprising an equivalent quantity of 10mg Pitavastatin calcium were weighed and little quantity of dimethyl formamide was added and remaining quantity of pH 6.8 phosphate buffer was added to make 10ml. The solution was filtered and 1ml of solution was transferred into 100ml volumetric flask and volume was made to 100ml with pH 6.8 phosphate buffer.^11,12 Then solution was analyzed with UV spectrophotometer at 245nm. The drug content was determined using calibration curve of pitavastatin calcium in pH 6.8 phosphate buffer.

Solubility studies:

Shake flask technique was used to study solubility of prepared solid dispersions, for each solid dispersion the set contains two separate 100ml conical flasks, 20ml of measured quantity of water and pH 6.8 phosphate buffer were added to respective flask. An excess quantity of solid dispersions were added until solid remains at bottom.^13,14 The flask was stirred for duration of 24-48 hours on a magnetic stirrer at rpm of 50. The presence of saturation was confirmed by visibility of excess material at flask bottom. The samples were filtered with 0.45μ whatman filter paper and analyzed using UV Spectrophotometer at λmax 245nm in water and pH 6.8 phosphate buffer.¹⁵

Micromeritic properties:

The flow properties of prepared solid dispersions were analyzed which indicates the ability of the solid dispersions to compress into a tablet in the further studies. The studies includes the following:

Bulk density:

Weighed quantity of prepared solid dispersions were transferred into a 50 ml measuring cylinder and the volume occupied by mass was noted as bulk volume, the formula to compute the parameter is the following.^16,17

Bulk density = –––––

V _o

M = Sample weight of solid dispersion (g),

V _o = bulk volume in ml of solid dispersion

Tapped density:

Weighed quantity of solid dispersions were transferred into a 50ml measuring cylinder.¹⁸ The cylinder was tapped using tapped density apparatus according to the procedure given in pharmacopeia and after the final tapped volume was noted as V _f.

Solid dispersion weight taken (g)

Tapped density = ––––––––––––––––––––––––––––

final tapped volume of solid dispersion (V_f)

Compressibility index (Carr’s Index): The difference between tapped density and bulk density is determined by computing Carr’s index. The difference will be higher in samples with poor flow properties.¹⁹ This difference could be determined by calculating Carr’s index in percentage.

Tapped density – Bulk density

Compressibility index (%) = –––––––––––––––––––––– × 100

tapped density

The angle of repose:

It was determined with fixed funnel method, where fixed quantity of formulated solid dispersions was poured into the funnel by closing its tip by adjustment of funnel height to 2.5cm.²⁰ The sample forms a pile as it flows from the funnel from which the diameter and radius were computed. The angle of reposes is determined by:

θ = tan^-1 × –––

h = funnel’s height in cm

r = circle’s radius in cm.

Hausner’s Ratio:

It is determined using following formula.²¹

Tapped Density

Hausner’s Ratio (H) = –––––––––––––––––

Bulk Density

Fourier transforms infrared (FT-IR) study:

The FT-IR spectra was analyzed for Pitavastatin Calcium, Beta Cyclodextrin, PVP K30, PEG 6000, physical mixtures of API with three carriers individually and for the prepared solid dispersions. The spectra was recorded using Agilent technologies FTIR spectral Analyzer²², the samples were placed on holder of analyzer and then spectra was run between the range according to IR functional group requirements up to 4000 cm^-1.

Differential scanning Calorimetry (DSC):

The DSC studies of API and its solid dispersion were analyzed. The procedure includes placing and sealing 2 – 4mg of sample into aluminum pans under inert nitrogen gas atmosphere.²³ The sample system was heated at constant temperature of 10°C/min. The temperature range was between 0- 270^oC and 0- 300^oC.

X-ray Diffractometry (XRD):

The crystallinity nature of samples were determined using powder XRD analysis.²⁴ The X-ray powder diffraction patterns were analyzed using Cu as anode material, with generator Settings at 30mA, 45kV, with an Intended Wavelength of Type - K-α1. The samples were scanned for 2 θ range up to 40⁰C.

Scanning electron microscope (SEM):

The morphology of pitavastatin and solid dispersion was obtained at suitable magnifications. The SEM images indicates surface morphology and pattern of powder sample operated at 3kV acceleration voltage.²⁵

In-Vitro Drug release studies of solid dispersions:

The drug release was determined by dissolution studies. Solid dispersions equivalent to 50mg of Pitavastatin calcium were taken and pH 6.8 phosphate buffer was used as dissolution media with USP type II apparatus.²⁶ (Rotating paddle type - Electrolab). The temperature was maintained at 37±0.5°C with rotating speed of 50 rpm. At specific time intervals of 5, 10, 15, 20, 25, 30 min 5ml sample was withdrawn and same volume of buffer was added. The samples were analyzed using UV-spectrophotometry at 245nm with pH 6.8 phosphate buffer as blank.

Stability study:

The stability study of formulated solid dispersions was done in accordance with ICH guidelines. The study was performed at accelerated conditions by sealing the formulations in closed containers at appropriated storage conditions. The drug content was analyzed at 0, 3 months.²⁷

RESULTS AND DISCUSSION:

Preformulation studies:

Preformulation studies were conducted for API and the results are displayed in table 2. The corresponding DSC, FTIR spectra and SEM, XRD results are represented in subsequent sections of results.

Drug excipient compatibility studies:

The pure API and physical mixture prepared by mixing 1:1 ratio of drug with carrier was subjected to compatibility studies by FTIR and stored in a stability chamber to maintain temperature and humidity conditions which is considered under physical observation method. The corresponding physical observation data is presented in the following table 3. The studies indicated API and carrier compatibility.

Table 2: Preformulation parameters of Pitavastatin calcium

S. No.	Test Parameter	Results observed
1.	Colour	White
2.	Odour	Odourless
3.	Physical state	Solid
4.	Bulk density	0.408g/ml
5.	Tapped density	0.476g/ml
6.	Compressibility index	14.2%
7.	Angle of repose	32.005⁰
8.	Solubility in water	0.88 mg/ml
9.	Solubility in pH 6.8 Phosphate buffer	2.15 mg/ml
10.	Solubility in 0.1 N Hcl	35 mg/ml
11.	Solubility in methanol	5.2 mg/ml
12.	Average Melting point	135.2 ⁰C
13.	DSC peak observation	134.5 ⁰c

Table 3: API and carrier compatibility study

S. No.	Material	Initial observation	40 ⁰C/ 75% RH (One month)	40 ⁰C/75% RH (three months)
1.	API	White colour solid	White colour solid	White colour solid
2.	API + PEG6000	White Colour blend	Complies	Complies
3.	API + PVP K30	White Colour blend	Complies	Complies
4.	API + Beta cyclodextrin	White Colour blend	Complies	Complies

Calibration curve of pitavastatin calcium in pH 6.8 Phosphate buffer:

A 1mg/ml stock solution of API was prepared in pH 6.8 phosphate buffer, from this stock solution, 10 µg/ml was prepared and λmax was determined to be 245 nm. Then the calibration curve was constructed, presented in figure 1.

Figure 1: Calibration curve of Pitavastatin calcium in pH 6.8 phosphate buffer

Practical Percentage yield and drug content:

The percentage yield and drug content of solid dispersions were evaluated and drug content was in range of 89.17 to 99.21. The results are tabulated in table 4. All solid dispersions exhibited presence of high drug content designating that these techniques are effective for preparation of solid dispersions.

Solubility studies:

The solubility studies indicated prepared solid dispersions exhibited improved solubility when compared to pure API. It is witnessed that increasing concentration ratio of carrier improved solubility, precisely with formulation PSD20, as beta cyclodextrin concentration increased solubility of Pitavastatin in water and 6.8 buffer increased. This could be due to conversion of crystalline molecule to reduced crystallanity and also due to reduction in particle size along with improved wetting. The results presented in table 5.

Table 4: Percentage yield and drug content of solid dispersions

Formulation code	Percentage yield (%)	Drug Content (%)
PSD1	90.18	90.02±0.09
PSD2	94.92	89.32± 0.17
PSD3	93.24	90.48± 0.10
PSD4	94.41	91.41± 0.07
PSD5	90.28	89.22± 0.10
PSD6	91.74	89.17± 0.08
PSD7	95.38	93.39± 0.13
PSD8	93.89	91.76± 0.12
PSD9	92.10	90.84± 0.11
PSD10	89.95	91.49± 0.14
PSD11	96.92	89.73± 0.21
PSD12	92.17	91.98± 0.12
PSD13	90.13	93.17± 0.18
PSD14	93.76	90.95± 0.10
PSD15	91.44	91.02± 0.17
PSD16	93.19	92.33± 0.25
PSD17	94.79	91.57± 0.14
PSD18	94.94	93.79± 0.07
PSD19	97.71	89.68± 0.25
PSD20	98.01	99.21±0.07
PSD21	96.29	91.41± 0.17
PSD22	97.79	91.06± 0.10
PSD23	90.15	89.92± 0.14
PSD24	93.26	92.67± 0.11

Data expressed as mean ± standard deviation (SD), n=3

Table 5: Solubility studies of Pitavastatin Calcium solid dispersions

Formulation code	Solubility in water (mg/ml)	Solubility in pH 6.8 phosphate buffer (mg/ml)
Pure API	0.88±0.021	2.15±0.115
PSD1	1.29±0.031	2.96±0.041
PSD2	1.51±0.019	4.09±0.086
PSD3	1.96±0.017	4.81±0.113
PSD4	2.11±0.017	5.05±0.121
PSD5	1.43±0.012	3.33±0.073
PSD6	1.74±0.012	4.41±0.121
PSD7	2.25±0.025	4.98±0.047
PSD8	3.09±0.036	7.94±0.045
PSD9	1.35±0.125	3.25±0.103
PSD10	1.63±0.016	4.30±0.024
PSD11	2.11±0.055	4.85±0.101
PSD12	2.37±0.073	5.31±0.065
PSD13	1.30±0.103	2.98±0.076
PSD14	1.49±0.124	4.10±0.111
PSD15	1.94±0.045	4.83±0.103
PSD16	2.15±0.129	5.19±0.095
PSD17	1.49±0.080	3.57±0.085
PSD18	1.75±0.082	4.45±0.069
PSD19	2.29±0.040	4.99±0.091
PSD20	3.58±0.021	8.89±0.024
PSD21	1.36±0.111	3.22±0.053
PSD22	1.62±0.102	4.29±0.052
PSD23	2.12±0.074	4.95±0.086
PSD24	2.39±0.023	5.48±0.052

Data expressed as mean ± standard deviation (SD), n=3

Micromeritic studies:

The studies displayed good flow properties. The corresponding results are visualized in table 6.

Table 6: Micromeritic properties of Pitavastatin Calcium olid dispersions

Formulation code	Bulk density (g/ml)	Tapped density (g/ml)	Angle of repose (0)	Carr’s index (%)	Hausner’s ratio
Pure API	0.408±0.008	0.476±0.007	32.005±0.16	14.28±0.64	1.16±0.008
PSD1	0.469±0.011	0.538±0.012	29.18±0.30	12.82±0.33	1.15±0.004
PSD2	0.478±0.013	0.546±0.013	28.11±0.13	12.45±0.52	1.14±0.006
PSD3	0.485±0.010	0.551±0.010	27.54±0.38	11.97±0.29	1.14±0.003
PSD4	0.482±0.006	0.549±0.008	27.23±0.28	12.25±0.20	1.14±0.002
PSD5	0.505±0.011	0.569±0.011	28.31±0.32	11.24±0.41	1.13±0.005
PSD6	0.513±0.012	0.568±0.011	25.65±0.49	9.74±0.71	1.11±0.008
PSD7	0.499±0.013	0.564±0.014	27.25±0.21	11.51±0.41	1.13±0.005
PSD8	0.512±0.011	0.576±0.010	26.46±0.33	11.11±0.34	1.12±0.004
PSD9	0.468±0.013	0.531±0.015	28.11±0.23	11.85±0.34	1.13±0.004
PSD10	0.462±0.009	0.528±0.012	26.93±0.20	12.48±0.34	1.14±0.004
PSD11	0.479±0.016	0.531±0.016	25.22±0.21	9.79±0.27	1.11±0.003
PSD12	0.465±0.008	0.529±0.009	28.02±0.20	12.09±0.22	1.14±0.002
PSD13	0.459±0.009	0.527±0.012	27.96±0.14	12.95±0.32	1.15±0.004
PSD14	0.483±0.009	0.559±0.012	28.57±0.22	13.58±0.40	1.16±0.005
PSD15	0.479±0.015	0.538±0.017	26.25±0.36	11.01±0.17	1.12±0.002
PSD16	0.491±0.014	0.555±0.012	28.08±0.18	11.53±0.79	1.13±0.010
PSD17	0.527±0.008	0.592±0.009	27.45±0.44	10.97±0.29	1.12±0.003
PSD18	0.526±0.011	0.597±0.015	26.33±0.38	11.88±0.34	1.13±0.004
PSD19	0.535±0.004	0.603±0.006	27.86±0.16	11.22±0.54	1.13±0.006
PSD20	0.548±0.007	0.605±0.010	25.92±0.17	9.42±0.32	1.11±0.004
PSD21	0.483±0.006	0.561±0.009	27.97±0.14	13.89±0.29	1.16±0.004
PSD22	0.479±0.013	0.539±0.012	28.93±0.19	11.07±0.36	1.12±0.004
PSD23	0.493±0.010	0.568±0.012	27.75±0.27	13.19±0.26	1.15±0.003
PSD24	0.488±0.005	0.541±0.006	24.37±0.44	9.79±0.35	1.11±0.004

Data expressed as mean ± standard deviation (SD), n=3

FTIR: The FTIR spectrum of Pitavastatin, physical mixture and solid dispersions are presented in figures 2, 3, 4.

Figure 2: FTIR spectrum of (A) Pitavastatin calcium (B) beta cyclodextrin (C) PVP K 30 (D) PEG600

Figure 3: FTIR spectrum of (A) Physical mixture of pitavastatin calcium and Beta cyclodextrin (B) pitavastatin calcium and PEG6000 (C) pitavastatin calcium and PVP k 30 (D) SD of PSD4

Figure 4: FTIR spectrum of (A) SD of PSD16 (B) PSD24 (C) PSD8 (D) PSD20

From the formulated solid dispersion batches the best suitable solid dispersion was selected based on criteria including the solubility in water and pH 6.8 phosphate buffer, PXRD analysis, SEM analysis and drug release dissolution studies in pH 6.8 phosphate buffer. The formulation PSD20 displayed high solubility in water and pH 6.8 phosphate buffer when compared to other formulations. The formulation PSD20 showed drug release of 98.91% in 30 min which is greater than other batches and the SEM analysis indicated that in this formulation conversion of API to porous form could have assisted in intensifying solubility and dissolution. The XRD pattern also showed that in this formulation the peak intensity and sharpness of peaks was reduced and few peaks were disappeared indicating that drug crystallinity has been reduced. Based on the above criteria and comparisons the formulation PSD20 was selected as best suitable solid dispersion specifically considering solubility and dissolution along with other supporting data.

Stability studies:

The Pitavastatin SD formulations were subjected for stability studies, at accelerated conditions in stability chamber and were collected at interval of 0, 3 months and analyzed for percentage drug content and dissolution. The results disclosed no witnessed significant changes in the appearance and in drug release, drug content.

CONCLUSION:

The present research attempts to evaluate that solid dispersions exhibits higher solubility and dissolution rates when compared to poorly water soluble drug. The SD were formulated by combining drug and carriers like PEG6000, PVP K 30, beta cyclodextrin in different ratios of 1:1, 1:2, 1:4, 1:6 using fusion method and kneading method. It reveals that the drug: carrier ratio has an impact on solubility, crystallinity, dissolution, percentage yield and drug content of prepared formulations. The reduction of crystallinity in prepared Solid dispersion were evident from XRD, SEM, DSC studies which indicates drug was suitably enclosed within carrier molecular matrix which helps in reducing crsyallinity of pure drug. The study also revealed carrier concentration has impact on solubility and dissolution enhancement, the formulation PSD20 presented high dissolution of 98.91% in 30 min and considered as best suitable formulation. It can be concluded that prepared solid dispersions can be considered as useful means for improving solubility and dissolution rates of Pitavastatin Calcium which can be further formulated into suitable dosage form like tablets.

REFERENCES:

1. Veer Patel, Rakesh Patel, Hetansh Shah, Shyam Purohit, Mayur Pawar, Abuzar Pathan. Solubility Enhancement of Azithromycin by Solid Dispersion Technique Using Mannitol and β-Cyclodextrin. Acta Scientific Pharmaceutical Sciences. 2021; 5(4): 48-54.

2. Khadka, P, Ro, J, Kim, H, Kim I, Kim J.T, Kim H, Cho J.M, Yun G, Lee J. Pharmaceutical particle technologies : an approach to improve drug solubility, dissolution and bioavailability. Asian Journal of Pharmaceutical Sciences. 2014; 9(6): 304- 316.

3. Manohar Kengar, Rohit Howal, Dattatray Aundhakar, Amit Nikam, Priyajit Hasabe. Physico-chemical Properties of Solid Drugs: A Review. Asian Journal of Pharmacy and Technology. 2019; 9(1): 53-9.

4. Sumit Kumar, Deepak Bhargava, Arti Thakkar, Saahil Arora. Drug carrier systems for solubility enhancement of BCS class II drugs : a critical review. Critical Reviews Therapeutic Drug Carrier Syst. 2013; 30(3): 217-256.

5. Vanita Rode P, Madhukar Tajne R. A Validated Stability-Indicating High-Performance Thin-Layer Chromatographic Method for the Analysis of Pitavastatin in Bulk Drug and Tablet Formulation. Asian Journal of Pharmaceutical Analysis. 2018; 8(1): 49-52.

6. Sneha D. Bhore. A Review on Solid Dispersion as a Technique for Enhancement of Bioavailability of Poorly Water Soluble Drugs. Research Journal of Pharmacy and Technology. 2014; 7(12): 1485-1491.

7. Nadia Saffoon, Riaz Uddin, Naz Hasan Huda, Kumar Bishwajit Sutradhar. Enhancement of Oral Bioavailability and Solid Dispersion: A Review. Journal of Applied Pharmaceutical Science. 2011; 1 (7): 13-20.

8. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. European Journal of Pharmaceutics and Biopharmaceutics. 2000; 50(1): 47-60.

9. Kalivoda A, Fischbach M, Kleinebudde P. Application of mixtures of polymeric carriers for dissolution enhancement of fenofibrate using hot-melt extrusion. International Journal of Pharmaceutics. 2012; 429: 58–68.

10. Ranim Alrouhayyah, Tatiana F. Sheshko, Svetlana N. Suslina. Improving the Dissolution rate of Mefenamic acid by preparing Solid Dispersions with Polyethylene glycol 4000. Research Journal of Pharmacy and Technology. 2023; 16(7): 3115-9. doi: 10.52711/0974-360X.2023.00512.

11. Vyas Jigar, Vyas Puja, Patel Jayvadan. Formulation and evaluation of solid dispersions of Rofecoxib for improvement of dissolution profile. African Journal of Pharmacy and Pharmacology. 2011; 5(5); 577-581.

12. Neha Sharma, Priyanka Ahirwar. Formulation and Characterization of Solid Dispersion of Oxcarbazepine. EAS Journal of pharmacy and Pharmacology. 2023; 5(3): 58-67.

13. 13, Talla S, Wadher K, Umekar M, Lohiya RT, Formulation, Optimization and Evaluation of Solid Dispersion of Deferasirox Using Factorial Design, Journal of Drug Delivery and Therapeutics. 2024; 14(5): 23-31.

14. Sharma Pravin Kumar, Sharma Pankaj Kumar, Darwhekar Gajanan N, Shrivastava Birendra. Formulation and evaluation of solid dispersion of Tadalafil. International Journal of Drug Regulatory Affairs. 2018; 6(1): 26-34.

15. Ganesh Chaulang, Piyush Patel, Sharwaree Hardikar, Mukul Kelkar, Ashok Bhosale, Sagar Bhise. Formulation and Evaluation of Solid Dispersions of Furosemide in Sodium Starch Glycolate. Tropical Journal of Pharmaceutical Research. 2009; 8(1): 43-51.

16. Desi Reddy RB, Neelima Rani T, Sindhuri SL, Bandhavi P, Anusha Rani T, Sowjanya Y. Formulation and In-vitro Evaluation of Simvastatin Solid Dispersions Research Journal of Pharmacy and Technology. 2012; 5(8): 1069-1071.

17. Dasari Nirmala, Ashok ChakradharP, Sudhakar M. Preparation and characterization of Pitavastatin solid dispersions. Research Journal of Pharmacy and Technology. 2016; 9(5): 555-558.

18. Ishtyaque Mikrani, Md. Raihan Sarkar, Mehedi Islam, Sreedam C. Das, Kazi Milenur Rahman Prattay. Development, Characterization and In vitro Evaluation of Solid Dispersion Formulations of Low Aqueous Soluble BCS Class II Drug Pitavastatin with Poloxamer 407 and HPMC. Dhaka University Journal of Pharmaceutical Sciences. 2022; 20(3): 325-336.

19. Komal Chandrakant Jadhav, Sourabh Sukumar Hegaje, Sadhana Uttam Jadhav, Rupesh Sopanrao Vaidhya, Mayuresh Ramesh Redkar. Formulation and Evaluation of Solid Dispersion of Poorly Soluble Drugs. Asian Journal of Pharmacy and Technology. 2022; 12(4): 309-312.

20. Alladi Saritha, Praveenachary A. Development and Characterization of Poloxamer Solid Dispersions of Cefuroxime Axetil. Research Journal of Pharmacy and Technology. 2015; 8(4): 360-4. doi: 10.5958/0974-360X.2015.00060.8

21. Praveen Parashar, Bharti Mangla, Suresh Kumar Joshi. Design and development of novel lipid based carrier system for delivery of pitavastatin calcium. International Journal of Pharmaceutical Sciences and Research. 2016; 7(12): 5030-5038.

22. Mahore J. G., Deshkar S. S., Kumare P. P. Solid Dispersion Technique for Solubility Improvement of Ketoconazole for Vaginal Delivery Research Journal of Pharmacy and Technology. 2019; 12(4): 1649-1654. doi: 10.5958/0974-360X.2019.00276.2

23. R.K. Surawase, K.G. Baheti, M.H. Dehghan. Application of Box Behnken Design for Development of Paliperidone Solid Dispersion using Fluid Bed Processing: Formulation and Characterization. Research Journal of Pharmacy and Technology. 2024; 17(8): 3567.

24. Jian Shen, Anna Hu, Yuxin Yang, Ting Nie, Siqi Huang, Zeneng Cheng, Wenjie Liu. Ternary solid dispersions of lacidipine: Enhancing dissolution and supersaturation maintenance through strategic formulation optimization. International Journal of Pharmaceutics. 2024: 654: 123989.

25. Ranim Saker, Wehad Ibrahim, Mohammad Haroun. Preparation and Evaluation of Nifedipine solid dispersions. Research Journal of Pharmacy and technology. 2020; 13(9): 4148-4152.

26. Viraj Kulthe V, Praveen Chaudhari D. Characterization of Etoricoxib Solid Dispersions Prepared By Spray Drying Technique. Research Journal of Pharmacy and Technology. 2010; (4): 1158-1166.

27. Venkates Kumar K, Arunkumar N, PRP Varma, Rani C, Neema George. Formulation and In Vitro Characterization of Valsartan Solid Dispersions. Research Journal of Pharmacy and Technology. 2009; 2(3): 502-506.

Received on 12.12.2024 Revised on 11.04.2025

Accepted on 01.07.2025 Published on 10.02.2026

Available online from February 16, 2026

Research J. Pharmacy and Technology. 2026;19(2):835-844.

DOI: 10.52711/0974-360X.2026.00119

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

S. No.	Observed peak	Functional group interpretation	Mode
1.	3065.73	O-H	Stretching
2.	3013.55	C-H	Stretching
3.	1636.30	C=O	Stretching
4.	1550.57	C=C	Stretching
5.	1213.24	C-O	Stretching
6.	1118.20	C-F	Stretching