INTRODUCTION:

The oral route of drug administration is the most common and preferred method of delivery due to convenience and ease of ingestion. From a patient’s perspective, swallowing a dosage form is a comfortable and a familiar means of taking medication. As a result, patient compliance and hence drug treatment is typically more effective with orally administered medications as compared with other routes of administration, for example, parenteral.^[1] More than 90% of drugs have poor solubility. It is estimated that 40% of active New Chemical Entities (NCEs) identified in combinatorial screening programs employed by many pharmaceutical companies are poorly water soluble.^[2] After administering a drug orally, it firstly dissolves in gastric and or intestinal fluids, and then permeates the membranes of the GI tract to reach systemic circulation.

Therefore, a drug with poor aqueous solubility will typically exhibit dissolution rate limited absorption, and a drug with poor membrane permeability will typically exhibit permeation rate limited absorption. Unfortunately, many of these potential drugs are abandoned in the early stages of development due to solubility concerns. It is therefore becoming increasingly more important that methods for overcoming solubility limitations be identified and applied commercially such that the potential therapeutic benefits of their active molecules can be realized. Poorly water-soluble drugs are increasingly becoming a problem in terms of obtaining the satisfactory dissolution within the gastrointestinal tract that is necessary for good bioavailability. It is not only existing drugs that cause problems but it is the challenge of medicinal chemists to ensure that new drugs are not only active pharmacologically but have enough solubility to ensure fast enough dissolution at the site of administration, often gastrointestinal tract. Dissolution of solid dosage forms in gastrointestinal fluids is a prerequisite to the delivery of the drug to the systemic circulation following oral administration. Dissolution depends in parts on the solubility of the drug substance in the surrounding medium. Surface area of drug particle is another parameter that influences drug dissolution, and in turn drug absorption, particle size is a determinant of surface area. Solubilization is the process by which the apparent solubility of a poorly water soluble substance is increased. Solubilization techniques include addition of a co-solvent, salt formation, Prodrug design, Complexation, particle size reduction, and the use of surface active agents (Micellization). Use of solvate and hydrates, polymorphs, hydrotrophy, use of absorbents, pH adjustment, solubilizing vehicles, etc. are the some other physicochemical approaches to enhancing oral absorption of poorly water soluble drugs.^[3]

Solid dispersions have been widely used to increase the dissolution rate, and hence improving the bioavailability of poorly water soluble drugs. They are defined as a dispersion of one or more active ingredients in an inert carrier or matrix in the solid state. Usually, a drug substance is incorporated into a water-soluble polymer, leading to a molecular, a crystalline or an amorphous dispersion of the drug. Although the metastable drug form dissolves faster than the crystalline state, the dissolution rate depends on the drug–polymer ratio.

Ramipril is adapted to the a-live metabolite Ramiprilat by alarmist esterase enzymes.ACE inhibitors, arrest the accomplishments of (ACE) angiotensin converting agitator, thus blurred the assembly of Angiotensin-II and as well abbreviating bradykinin breakdown. Abatement in Angiotensin-II after-effects in alleviation of arterial bland beef arch to abatement in absolute borderline resistance, because abbreviation claret burden of blood as blood claret is forced through vessels of blood. Showing converting enzyme inhibitor reduces angiotensin-II which is circulating and cause potent vasodilator bradykinin increase.

MATERIAL AND METHOD:

Melting Point Determination:

Ramipril melting point was determined using Capillary technique by melting point apparatus used. One side of capillary was sealed with the help of burner flame. Then small quantity of drug was filled in capillary by open side and capillary was attached to the melting point apparatus. Thermometer was checked for no any error and placed in dedicated position of melting point apparatus. Then melting point apparatus was started and temperature was raised gently. The temperature at which sample got melt and reading was noted as a melting point.

Solubility Determination:^[4,5]

An excess amount of Ramipril was placed in volumetric flask containing 20 ml of solvent. The volumetric flask were thoroughly shaken from mechanical shaker for 24 hrs and kept aside for 24 hrs at room temperature. At the end of this period the solution were filtered and filtrate was collects into dry containers. The solution were suitably diluted and assayed by UV-Spectrophotometric λmax after suitable dilution.

Determination of λmax:

Accurately weighed 10 mg of Ramipril was transferred to 100 ml volumetric flask and dissolved in 0.1 N HCL (pH 1.2) to obtained concentration of 100μg/ml and which was further diluted to obtain the concentration of 1 μg/ml. The 1 μg/ml solution in 0.1 N HCL (pH 1.2) was scanned against wavelength 200-400 nm in spectrum mode and maximum absorbance of solution was observed. The absorbance of 1μg/ml solution was measured against 0.1 N HCL (pH 1.2) as blank. The λmax was determined in UV-Visible spectrophotometer.

Preparation of Calibration Curve: ^[6,
7]

· Stock solution of Ramipril were prepared by dissolving 100 mg of drug in small amount of methanol and volume was make up to 100ml of volumetric flask to get the concentration of 1000μg/ml.

· After that from 1000 μg/ml solution withdrawn 10 ml of solution and kept in 100 ml of volumetric flask and volume make up to 100 ml with solvent (0.1 N HCL, Water and Methanol) to get the concentration of 100μg/ml.

· From 100μg/ml solution withdrawn 10 ml of solution and kept in 100 ml of volumetric flask and volume make up to 100 ml with solvent (0.1 N HCL, Water and Methanol) to get the 10μg/ml.

· From 10 μg/ml solution withdrawn 1, 2, 3, 4, 5 and 6 ml were kept in 10 ml of volumetric flask and volume make up to 10 ml with solvent (0.1 N HCL, Water and Methanol) to get the final concentrations 1, 2, 3, 4, 5 and 6 μg/ml respectively. The λmax was determined in UV and followed by standard calibration curve.

Drug –Polymer Compatibility Study:

The IR spectrum of Ramipril and the solid dispersion ratio of 1:2 of PVP K30 and PEG 4000 were recorded in the stretching frequency range 400-4000 cm-1. The samples were prepared by KBr press pellet technique. Drug and polymer compatibility testing was performed by mixing drug and polymer in equal proportion and the IR grade was noted for mixture. 2-3 mg of sample was mixed with previously dried IR grade potassium bromide and kept in sample cell. The cell was then fitted in sample holder, spectra were recorded with FT-IR instrument and the spectral analysis was done. KBr as a standard (blank).

Preparation of Solid Dispersion:

Solid dispersions of Ramipril were prepared by solvent evaporation method. Ramipril with polymers PEG 4000 and PVP K30 taken in different ratio (1:1, 1:2, and 1:3) and then dissolved in sufficient volume of methanol with continuous stirring. The solvent was then completely evaporated with continuous stirring on water bath and finally obtained dry mass at room temperature. The final solid mass is crushed and pulverized using mortar and pestle, then passed through 24 mesh sieve. Prepared solid dispersion stored in desiccator until used for further studies.

Determination of Drug Content of Solid Dispersion:

Weighed accurately solid dispersion equivalent to 50 mg of Ramipril and transferred to 50 ml of volumetric flask and volume was making up to the 50 ml of phosphate 0.1 N HCL (pH 1.2). From this 1 ml was taken in 10 ml volumetric flask and volume adjusted up to 10 ml of 0.1 N HCL (pH 1.2). The absorbance of the solution was measured at 222 nm using appropriate blank. The drug content of Ramipril was calculated using calibration curve.

Determination of Solubility of Solid Dispersion: ^[8,9]

The solubility of the various solid dispersions was determined in water. Excess of sample was transferred to flask before adding water. The mixtures then placed in mechanical shaker maintained at 37ºC for 48 hrs. The sample were filtered through filter paper and assayed by UV- spectrophotometry after suitable dilution.

Preformulation Study of Various Solid Dispersions and Tablet Powder Mixtures: ^{[10, 11]}

The blend was evaluated for following parameters.

(i) Bulk Density:

Bulk density of the granules was determined by pouring gently 5 gm of sample through a glass funnel into 25 ml graduated cylinder. The volume occupied by the sample was recorded; the bulk density was calculated by the following formula.

Mass of the powder (M)

Bulk density (ρb) = ------------------------------

Volume of the bulk powder (Vb).

(ii) Tapped Density:

About 5 gm of granules was poured gently through a glass funnel into a 25 ml graduated cylinder. The cylinder was properly placed in the bulk density apparatus to tapped from height of 2 inches until a constant volume was obtained. Volume occupied by the sample after 300 tappings were recorded and tapped density was calculated by the equation.

Do = M / Vp

Where, Do = bulk density

M = weight of samples in grams

Vp = final tapped volumes of granules in cm³

(iii) Carr’s Index:

One of the important measures that can be obtained from bulk and tapped density determinations is the percent compressibility or carr’s index (C.I.) which is determined by the equation.

(Tapped density- Bulk density)

% Compressibility= -------------------------------- x 100

Tapped density

(iv) Hausner Ratio:

The Hausner ratio can be determined using the following formula:

Tapped density

Hausner ratio(%) = --------------------- x 100

Pour density

(v) Angle of Repose:

The angle of repose of each powder blend was determined by glass funnel method. Powders were weighed accurately and passed freely through the funnel so as to form a heap. The height of funnel was so adjusted that the tip of funnel just touched the apex of the heap. The diameter of the powder cone so formed was measured and the angle of repose was calculated by using the following formula.

Tan θ = h/r

Where, h = height of the powder cone; r = radius of the powder.

Formulation of Tablet: ^[12]

By Using Direct Compression Method:

Three formulations of solid dispersion ratio 1:2 PVP K30 and three formulations of solid dispersion ratio 1:2 PEG 4000 of fast dissolving tablets of Ramipril were prepared by taking solid dispersion ratio 1:2 of PVP K30 (25.02 mg) and 1:2 ratio of PEG 4000 (19.47 mg) equivalent to 10 mg of Ramipril. In each formulations Superdisintegrants like Crospovidone was added and mixed for 10 min.. The above mixture were passed through sieve no.#60. Lubricant like magnesium stearate, glidant like talc were added and the whole powder mixture passed through sieve no.#60. After that diluents like lactose was added. The whole bulk powder was then mixed thoroughly for 15 min in mortar. The powder was then compressed into round shaped tablets on tablet punching machine. The weight of tablets in each batch was kept constant. All the batches of 100 tablets were prepared by direct compression using tablet compression machine.

Formulation Batches (F1-F6) of Fast Dissolving Tablets of Ramipril:

Table.No.1 Design of different formulation batches of fast dissolving tablets of Ramipril

Sr.No	Ingredients (mg)	Formulation code (qty/tab in mg)
Sr.No	Ingredients (mg)	F₁	F₂	F₃	F₄	F₅	F₆
1	Solid dispersion	25.02	25.02	25.02	19.47	19.47	19.47
2	Crospovidone	50.2	60.2	70.2	50.2	60.2	70.2
3	Magnesium Stearate	2	2	2	2	2	2
4	Talc	0.8	0.8	0.8	0.8	0.8	0.8
5	Lactose	0.8	0.8	0.8	0.8	0.8	0.8
6	Total Weight	21.18	11.18	1.18	26.73	16.73	6.73

Evaluation of Tablet: ^[13,14,15]

· Hardness :

The resistance of tablets to shipping or breakage under conditions of storage, transportation and handling before usage depends on its hardness. The hardness of tablet was measured by Monsanto hardness tester. The hardness was measured in terms of kg/cm².

· Thickness :

Thickness and diameter of tablets were important for uniformity of tablet size. Thickness and diameter was measured by using vernier caliper.

· Friability :

Friability is the measure of tablet strength. Roche friabilator was used for testing the friability. Ten tablets were weighed accurately and placed in the tumbling apparatus that resolves at 25 rpm dripping the tablets through a distance of six inches with each revolution. After 4 minutes, the tablets were weighed and the percentage loss in tablet weight was determined.

Initial weight – Final weight

% Friability = ----------------------------------------× 100

Initial weight

· Weight Variation Test :

To find out weight variation, 20 tablets of each type of formulation were weighed individual tablet weight was then compared with average value to find the deviation in weight.

Table No. 2 Specification for tablet as per Indian Pharmacopoeia – 2017

Sr. No.	Average weight of tablet	% Deviation allowed
1.	80 mg or less	10
2.	More than 80 mg but less that 250 mg	7.5
3.	250 mg or more	5

· Determination of Drug Content of Tablet:

Three tablets of each type of formulation were weighed and crushed in mortarand powder equivalent to 10 mg of Ramipril tablet was weighed and dissolved in 100 ml of 0.1 N HCL (pH 1.2) this was the stock solution from which 1 ml sample was withdrawn and diluted to 10 ml with 0.1 N HCL (pH 1.2). The absorbance was measured at wavelength 222 nm using double beam UV-Visible Spectrophotometer.

· Disintegration Time:

The disintegration apparatus was used for the study. It contains 2 basket rack assembly. Each basket rack assembly consists of 6 glass tubes that are 3 inches long, open at the top and held against 10 mesh screen at the bottom. Each tablet was placed in each tube and the basket rack was positioned in 1-L beaker of distilled water. The 37± 2ºC temperature was maintained throughout the study.

· In vitro Dissolution studies of Ramipril Tablet:

The in-vitro drug release was determined using USP dissolution testing apparatus type –II (paddle type). The dissolution test was performed using 900 ml of 0.1 N HCL (pH 1.2) at 37ºC ± 0.5ºC and 50 rpm. Sample volume of 5 ml was withdrawn at regular time intervals of 5, 10, 15, 20, 25, 30, 35 and 40 min. from a zone midway between the surface of dissolution medium and the top of rotating paddle not less than 1 cm apart from the vessel wall. The volume withdrawn was replaced by fresh volume of dissolution medium to maintain constant volume of medium. The filtered samples were analyzed spectrophotometrically at 222 nm using 0.1 N HCL (pH 1.2) as a blank. Drug content in dissolution sample was determined by calibration curve.

RESULT AND DISCUSSION:

Characterization of Ramipril:

· Physical Tests:

It included the state, color; odor and melting point were done.

Table No.3 Characterization of Ramipril

Sr. No.	Characters	Inference
1	State	Crystalline powder
2	Color	White
3	Odor	Odorless
4	Melting Point	107ºC-109 ºC

The characterization of Ramipril was inspected by visual eye and it was observed that state was crystalline powder, color was white, odor was odorless and the melting point of Ramipril was measured and it was found to be 107ºC-109 ºC. They were compared with pharmacopoeial standards it was found within acceptance limits.

· Solubility Of Ramipril:

Table No.4 Solubility of Ramipril In Different Solvents

Sr. No.	Sample	Solubility of Ramipril (mg/ml)
Sr. No.	Sample	Distilled water	Methanol	Ethanol
1.	Pure Drug	0.040mg/ml	1.3 ± 0.02	0.831 ± 0.03

Ramipril was found to be poorly water soluble in water, slightly soluble in methanol and very slightly soluble in ethanol. The solubility of Ramipril was compared with the pharmacopoeial standard it was found within acceptance limits.

Spectrophotometric Characterization:

· λ_maxDetermination:

1 µg/ml solution in 0.1 N HCL (pH 1.2) was scanned against wavelength 200-400 nm in spectrum mode and maximum absorbance of solution was observed at 222 nm as shown in fig.no.1.

Fig.No.1. Determination of λ_max

Preparation of Calibration Curve of Ramipril:

The calibration curve of Ramipril was prepared in 0.1 N HCL (pH 1.2) solution. Ramipril showed maximum absorption at wavelength 222 nm. The straight line obtained in the 0.1 N HCL (pH 1.2) had a regression coefficient of 0.994 as shown in fig.no.1. Linearity was found in the concentration range 1-6 µg/ml. Other details of calibration curve are given below.

Y = mx + c

Y = 0.160x + 0.041

Where,

Y = absorbance

m = slope

x = concentration in µg/ml.

c = Y-intercept

Table No.5 Absorbance of various concentrations of Ramipril in 0.1N HCL (pH 1.2)

Sr.No.	Concentration (µg/ml)	Absorbance at 222 nm
1	0	0
2	1	0.2143
3	2	0.3863
4	3	0.5417
5	4	0.7105
6	5	0.8239
7	6	0.9831

Fig.No.2. Calibration Curve of Ramipril in 0.1 N HCL (pH 1.2)

The prepared calibration curve in 0.1 N HCL (pH 1.2) obeyed Beer’s and Lambert’s law in the concentration range of 1-6 µg/ml. The value of regression coefficient are 0.994 shows the linearity relationship between concentration and absorbance. (Fig.no.2)

Drug – Polymer Compatibility Studies:

· Fourier Transform- Infra Red Spectrophotometer Study:

The pure drug Ramipril and solid dispersion ratio of drug and polymer was characterized by the FTIR spectral analysis for any physical and chemical alteration of the drug characteristics. The FTIR spectra of Ramipril in fig.no.3, Solid dispersion ratio of 1:2 of PEG 4000 in fig.no.4 and Solid dispersion ratio of 1:2 of PVP K30 in fig.no.5. Comparision of peaks of different functional group are tabulated in table no.6

Fig. No.3 FTIR Spectra of Ramipril

Fig.No.4 FTIR Spectra of Solid dispersion 1:2 Ramipril:PEG 4000

Fig.No.5 FTIR Spectra of Solid dispersion 1:2 Ramipril:PVP K30

Table No.6 Comparision of The Peaks of Functional Groups Observed in IR Spectra of Compatibility Studies

IR Spectra	Peak of Functional Groups [Wavelenght (cm^-1)]
IR Spectra	C-H Bending (Aromatic)	O-H Bending (alcohol) and C-O (ethers,alcohol,esters) and C-N (amines)	C-O Stretching (alcohol)	N-H Bending	C=N Stretching and C=O Stretching (amides)	C=O (aldehyde, ketone and esters)
Reference Standard	700-850	1050-1150 1050-1400	1250-1300	1500-1650	1630-1690 1650-1700	1720-1740, 1690-1750, 1735-1750
Ramipril	752.24	1099.43	1274.95	1651.07	1651.07	1741.72
1:2 PEG 4000	752.24	1109.07	1278.81	1651.07	1651.07	1739.79
1:2 PVP K30	750.31	1109.07	1282.66	1658.78	1658.78	1743.65

· Drug Content (%) of Various Solid Dispersion:

Table No.8 Drug content (%) of solid dispersion

Sr. No.	Solid Dispersion Ratio’s	Drug Content (%)
1	(1:1) PVP K30 [S.D.1]	96.0 %
2	(1:2) PVP K30 [S.D.2]	99.3 %
3	(1:3) PVP K 30 [S.D.3]	96.3 %
4	(1:1) PEG 4000 [S.D.4]	95.5 %
5	(1:2) PEG 4000 [S.D.5]	99.8 %
6	(1:3) PEG 4000 [S.D.6]	97.0 %

The drug content of different ratio of solid dispersion was found to be within the limit (95-100 %). From above table no.15 the drug content was observed in 1:2 ratio of PVP K30 (S.D.2) the drug content was found to be 99.3 % more satisfactory as compared to S.D.1 and S.D.3. Similarly in 1:2 ratio of PEG 4000 (S.D.5) the drug content was found to be 99.8 % more satisfactory as compared to S.D.4 and S.D.6.

· Solubility Study of Various Solid Dispersion:

Table No.9 Solubility of Various Solid Dispersion

Sr. No.	Solid Dispersion Code	Solubility (mg/ml)
1	(1:1) PVP K30 [S.D.1]	0.739 ± 0.39
2	(1:2) PVP K30 [S.D.2]	1.35 ± 0.61
3	(1:3) PVP K 30 [S.D.3]	0.961 ± 0.37
4	(1:1) PEG 4000 [S.D.4]	0.983 ± 0.53
5	(1:2) PEG 4000 [S.D.5]	1.40 ± 0.71
6	(1:3) PEG 4000 [S.D.6]	1.29 ± 0.48

The solubility of different ratio of solid dispersion was found to be in table no.16 the solubility was observed in 1:2 ratio of PVP K30 (S.D.2) was found to be 1.35 ± 0.61 (slightly soluble) more satisfactory as compared to 1:1 and 1:3. Similarly in 1:2 ratio of PEG 4000 (S.D.5) the solubility was found to be 1.40 ± 0.71 (slightly soluble) more satisfactory as compared to S.D.4 and S.D.6.

On the basis of drug content and solubility of solid dispersion we proceeded to tablets formulation for the solid dispersion of 1:2 ratio of PVP K30 (S.D.2) and 1:2 ratio of PEG 4000(S.D.5) because it showed the best drug content and solubility.

Preformulation Studies of Tablet Powder Mixtures:

The prepared powder mixtures were evaluated for the blend property like bulk density, tapped density, Carr’s index, Hausner’s ratio and angle of repose. Results obtained are given in table no.10

Other parameters like disintegration time, diameter and drug content were also determined. The disintegration time was determined by disintegration apparatus and was found to be within the range of 28 to 54 sec which is the expected range for fast dissolving tablets. The % Drug contents of tablets from each batch was determined by UV Spectrophotometric method at wavelength 222 nm. The results showed drug content in the range of 96.25 % to 99.36 % which was within the acceptable Pharmacopoeia limits. All these results were tabulated in table no.12.

Table No.12 Results of Disintegration Time, Drug Content and Diameter of Fast Dissolving Tablet of Ramipril

Parameters	Disintegration time (sec) (Mean, ±S.D)	Drug content (%) (Mean, ±S.D)	Diameter (cm) (Mean, ±S.D)
Batches	Disintegration time (sec) (Mean, ±S.D)	Drug content (%) (Mean, ±S.D)	Diameter (cm) (Mean, ±S.D)
F1	54 ± 0.171	96.25 ± 0.43	0.6
F2	50 ± 0.124	97.25 ± 0.35	0.6
F3	41 ± 0.194	98.94 ± 0.60	0.6
F4	33 ± 0.125	97.25 ± 0.43	0.6
F5	32 ± 0.134	98.56 ± 0.61	0.6
F6	28 ± 0.124	99.36 ± 0.62	0.6

Mean, ±S.D. n=3

In-vitro dissolution study of Formulations:

In-vitro drug dissolution studies were carried out in 0.1 N HCL (pH 1.2) using USP dissolution test apparatus II. Temperature was set 37º C ± 0.5º C and the samples were withdrawn at 5 min to 40 min. Study was carried out in triplicate. The results were tabulated below.

Table No.13 Cumulative Percentage Drug Release of All Formulation Batches

Time (min)

% CDR of all formulations

22.86

± 0.81

24.36

±0.43

25.65

± 0.37

30.68

± 0.62

33.29

± 0.14

36.58

± 0.64

34.12

±0.58

36.84

± 0.53

38.54

± 0.68

40.49

± 0.34

42.61

± 0.68

46.52

± 0.77

42.21

± 0.14

46.57

± 0.07

50.41

± 0.10

56.08

± 0.07

58.25

± 0.08

61.21

±0.81

57.14

± 0.70

60.14

± 0.13

63.05

± 0.18

72.29

± 0.13

75.91

± 0.27

78.34

± 0.72

65.24

± 0.11

68.25

± 0.25

71.58

± 0.45

76.78

± 0.16

79.56

± 0.15

82.19

± 0.43

71.15

± 0.45

74.24

±0.09

77.24

± 0.05

82.97

± 0.18

85.46

± 0.54

88.26

± 0.14

78.54

± 0.72

81.98

± 0.23

85.06

± 0.39

89.05

± 0.11

91.08

± 0.54

95.09

± 0.89

82.87

± 0.24

86.25

± 0.43

88.78

± 0.54

92.02

± 0.58

94.55

± 0.77

97.68

± 0.91

Mean, ±S.D. n=3

The F6 batch containing the solid dispersion (1:2) and in which drug Ramipril and polymer polyethylene glycol 4000. The F6 batch showed percentage drug release was found to be 97.68 % in 40 min. From above fig.no.6 it was compared the drug release of remaining formulations F1-F5 showed 82.87 % to F5 showed 94.55 % in 40 min. All formulations Containing same quantity of superdisintegrants like Crospovidone and Sodium starch glycolate was used. From fig.no.6 it was clearly concluded that the F6 batch containing PEG 4000 shows more effect on solubility and drug release profile of Ramipril by solvent evaporation technique than PVP K30.

CONCLUSION:

The present work was carried out to enhance the solubility of Ramipril by solid dispersion technique and develop fast dissolving tablet of Ramipril. The study has introduced that the solid dispersion of Ramipril with water soluble carriers Polyvinyl pyrrolidone K30 and Polyethylene glycol 4000 was changed the crystallinity of Ramipril. Fast dissolving tablet of Ramipril was developed by using solid dispersion 1:2 PVP K30 (S.D. 2) and PEG 4000 (S.D. 5) and Crospovidone as a superdisintegrants by direct compression technique. Solubility was found to higher when Polyethylene glycol 4000 was used as a carrier with ratio 1:2 in solid dispersion. In-vitro release of optimized formulation of fast dissolving tablets of Ramipril F6 was found 97.68% drug release in 40 min. and disintegration time being 28 sec. So it was concluded that fast dissolving tablet of Ramipril (F6) containing PEG 4000 as a polymer in solid dispersion (1:2) and Crospovidone as a superdisintegrant shows best results in terms of percent drug release and disintegration time. Hence solubility can be enhanced for Ramipril, for fast disintegration and best percent drug release.

REFERENCES:

1. Ohara T, Dissolution mechanism of poorly water-soluble drug from extended release solid dispersion system with ethylcellulose and hydroxypropylmethyl cellulose. Int. J. Pharm.302, 2005, 95–102

2. Lewis S.,Udupa N., Dhirendra K., Atin K., Solid Dispersions. J. P. Ed. Pharm. Sci., 2009, Vol. 22, 234-246

3. Serajuddin, Abu, T.M., (1999); solid dispersion of poorly water-soluble drugs early promises, subsequent problems, and recent breakthroughs, Journal of Pharmaceutical Science, 1999, 88

4. https://en.wikipedia.org/wiki/Talc.

5. https://en.wikipedia.org/wiki/Lactose.

6. Wanare Ravi S, ”Enhancement of Dissolution Rate of Poorly Water Soluble Drug by Solid Dispersion Technique”, Research journal of pharmaceutical biological and chemical sciences, April-june 2013, RJPBCS volume 4 issue 2, 686.

7. Chander Harish, Kumar Sachin, Bhatt Bineets,” Formulation And Evaluation Of Fast Dissolving Tablet Of Ramipril”, pelegia research library, Der pharmacia sinica 2011, 2 (6), 163-170

8. Owusu G, Habib M.J, Polymers Applied in Solid Dispersion Technology. In, Clinical Research and Regulatory Affairs, Informa Healthcare, 1998; Vol. vol.1, 25-45

9. Van Drooge D.J, Hinrichs W.L, Frijlink H.W, Incorporation of Lipophillic Drug in Sugar Glasses by Lyophilization Using a Mixture of Water and Tertiary Butyl alcohol as Solvent. J. Pharm. Sci., 2004, 713-725

10. Martin’s Js, Physical Pharmacy and Pharmaceutical Sciences, 5^th Ed., Lippincott Williams and Wilkins Philadelphia, 2004, 25-54.

11. Chandrakant D.S, Danki Lingaraj S, Sayeed Abdul, Kinagi Mallikarjun B, Preparation and evaluation of inclusion complexes of water insoluble drug, International Journal of Research in Pharmaceutical and Biomedical Sciences, Vol. 2(4) Oct - Dec 2011, 1599-1616.

12. Deshpande S.V, Kapse B.P, Patil A.R, Mr.Sapkal, Sapkal D.S, “ Enhancement Of Solubility Study Of Poorly Water Soluble Drug By Solid Dispersion Techniques, International journal of research in IT, management and engineering, ISSN 2249-1619, volume 6, Issue 05, May 2016, 45-55.

13. United States Pharmacopoeia and National formulary, 24^th Asian Edition, The United States Pharmacopoeia Convention Inc., U.S.A., 2009, 2446-2448.

14. Indian Pharmacopoeia, Ministry Of Health And Family Welfare, New Delhi, Controller of Publication, 4^th Edition, 2007,Volume 2, 659-61.

15. Lachman L, Liberman H.A, Joseph L.K, The theory and practice of Industrial pharmacy, 4^th ed. India, Varghese publishing house, 203-301.

Received on 01.03.2019 Modified on 16.04.2019

Research J. Pharm. and Tech 2019; 12(8): 3764-3772.

DOI: 10.5958/0974-360X.2019.00645.0

Solid Dispersion	Bulk Density (gm/cm³) (Mean, ±S.D)	Tapped Density (gm/cm³) (Mean, ±S.D)	Carr’s Index (%) (Mean, ±S.D)	Hausner’s Ratio (gm/cm³) (Mean, ±S.D)	Angle of Repose (q) (Mean, ±S.D)
(1:1) PVP K30 [S.D.1]	0.589±0.51	0.659± 0.18	10.56±0.90	1.11± 0.81	9.45±0.30
(1:2) PVP K30 [S.D.2]	0.599±0.71	0.670± 0.39	10.53±0.30	1.11±0.78	11.87±0.07
(1:3) PVP K 30 [S.D.3]	0.556±0.77	0.628± 0.68	11.43±0.80	1.12± 0.91	13.56±0.61
(1:1) PEG 4000 [S.D.4]	0.518±0.58	0.535± 0.71	6.66±0.60	1.07±0.14	4.94±0.77
(1:2) PEG 4000 [S.D.5]	0.481±0.50	0.521± 0.65	7.68± 0.70	1.08±0.32	8.98±0.96
(1:3) PEG 4000 [S.D.6]	0.439±0.60	0.478± 0.89	8.18± 0.70	1.08±0.90	12.09±0.55
Mean, ±S.D., n=3

Parameters	Bulk Density (gm/cm³) (Mean, ±S.D)	Tapped Density (gm/cm³) (Mean, ±S.D)	Carr’s Index (%) (Mean, ±S.D)	Hausner’s Ratio (gm/cm³) (Mean,±S.D)	Angle of Repose (q) (Mean,±S.D)
Batches	Bulk Density (gm/cm³) (Mean, ±S.D)	Tapped Density (gm/cm³) (Mean, ±S.D)	Carr’s Index (%) (Mean, ±S.D)	Hausner’s Ratio (gm/cm³) (Mean,±S.D)	Angle of Repose (q) (Mean,±S.D)
F1	0.562 ± 0.60	0.631 ± 0.08	10.93 ± 0.46	1.12 ± 0.90	11.31 ±0.90
F2	0.561 ± 0.89	0.622 ± 0.67	9.80 ± 0.43	1.10 ± 0.78	12.40 ± 0.82
F3	0.568 ± 1.13	0.634 ± 0.55	10.41 ± 0.82	1.11 ± 0.89	13.50 ±0.58
F4	0.557 ± 0.80	0.622 ± 0.98	10.20 ± 0.88	1.11 ± 0.64	12.68 ±0.44
F5	0.552 ± 0.02	0.625 ± 1.14	10.11 ± 0.97	1.13 ± 0.76	12.50 ±0.18
F6	0.572 ± 0.25	0.630 ± 0.11	9.20 ± 0.76	1.10 ± 0.55	13.92 ±0.84

Parameters	Weight Variation (mg) (Mean, ±S.D)	Thickness (mm) (Mean,±S.D)	Hardness (kg/cm²⁾ (Mean,±S.D)	Friability (%) (Mean, ±S.D)
Batches	Weight Variation (mg) (Mean, ±S.D)	Thickness (mm) (Mean,±S.D)	Hardness (kg/cm²⁾ (Mean,±S.D)	Friability (%) (Mean, ±S.D)
F1	100.32 ± 0.50	0.5 ± 0.11	2.25 ± 0.20	0.549 ± 0.082
F2	100.29 ± 0.20	0.5 ± 0.09	2.27 ± 0.48	0.409 ± 0.093
F3	100.32 ± 0.25	0.5 ± 0.05	2.58 ± 0.50	0.549 ± 0.082
F4	100.17 ± 0.20	0.5 ± 0.11	2.81 ± 0.85	0.291 ± 0.009
F5	100.19 ± 0.12	0.5 ± 0.05	2.90 ± 0.45	0.449 ± 0.091
F6	100.12 ± 0.30	0.5 ± 0.09	2.90 ± 0.48	0.678 ± 0.301